Management of Nonmalignant Portal Vein Thrombosis in Cirrhosis.

Nonmalignant portal vein thrombosis (PVT) is a common complication of cirrhosis especially at the stage of decompensations. The diagnosis of PVT in cirrhosis is often incidental and it may be detected during routine semestral abdominal ultrasound with Doppler during screening for hepatocellular carcinoma or during hospitalization for decompensated cirrhosis. After detection of PVT on abdominal ultrasound, it is important to evaluate patients with cross-sectional imaging to determine the age of thrombus, whether acute or chronic, the extent and degree of luminal occlusion of the portal vein, and to rule out hepatocellular carcinoma or other underlying malignancy. Factors influencing management include the degree and extent of luminal occlusion of PVT, potential listing for liver transplantation, and portal hypertension (PHT) complications such as variceal hemorrhage and refractory ascites, severity of thrombocytopenia, and other comorbidities including chronic kidney disease. Anticoagulation is the most common therapeutic option and it is specially indicated in patients who are candidates for liver transplantation. Interventional procedures including transjugular intrahepatic portosystemic shunt (TIPS) placement and mechanical thrombectomy may be used on a case-by-case basis in patients with contraindications or adverse events related to anticoagulation, who develop worsening PVT while on anticoagulant therapy, or have chronic PVT and PHT complications that are not manageable medically or endoscopically.

A trombose da veia porta (TVP) é uma complicação frequente na cirrose, especialmente na fase de descompensação. O diagnóstico é na maioria das vezes realizado de forma incidental. durante o rastreio semestral para o carcinoma hematocelular com ecografia abdominal com doppler ou durante o internamento por episódio de descompensação da cirrose. Após a deteção de TVP numa ecografia abdominal com doppler, é importante a realização de um método de imagem complementar de corte axial para avaliar a idade do trombo, se agudo ou crónico, a extensão e grau de oclusão luminal da veia porta e para excluir carcinoma hepatocelular ou outra neoplasia subjacente. A gestão do doente depende do grau de oclusão e da extensão do trombo na circulação portal, mas também da possibilidade de ser candidato para transplante hepatico, complicações da hipertensão portal, gravidade de trombocitopenia e da existência de outras comorbilidades relevantes como a doença renal crónica. A anticoagulação é a principal opção terapêutica mas outros procedimentos como a colocação de TIPS e trombectomia mecânica devem ser pensados caso a caso, quando existem contra-indicações à anticoagulação, a resposta à terapêutica anticoagulante não é adequada ou existem complicações da hipertensão portal não abordáveis com terapêutica médica ou endoscópica.

Predicting survival in patients with 'non-high-risk' acute variceal bleeding receiving ß-blockers+ligation to prevent re-bleeding.

BACKGROUND & AIMS: Pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for high-risk acute variceal bleeding (AVB; i.e., Child-Turcotte-Pugh [CTP] B8-9+active bleeding/C10-13). Nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation for secondary prophylaxis. We investigated prognostic factors for re-bleeding and mortality in 'non-high-risk' AVB to identify subgroups who may benefit from more potent treatments (i.e., TIPS) to prevent further decompensation and mortality. METHODS: A total of 2,225 adults with cirrhosis and variceal bleeding were prospectively recruited at 34 centres between 2011-2015; for the purpose of this study, case definitions and information on prognostic indicators at index AVB and on day 5 were further refined in low-risk patients, of whom 581 (without failure to control bleeding or contraindications to TIPS) who were managed by non-selective beta-blockers/endoscopic variceal ligation, were finally included. Patients were followed for 1 year. RESULTS: Overall, 90 patients (15%) re-bled and 70 (12%) patients died during follow-up. Using clinical routine data, no meaningful predictors of re-bleeding were identified. However, re-bleeding (included as a time-dependent co-variable) increased mortality, even after accounting for differences in patient characteristics (adjusted cause-specific hazard ratio: 2.57; 95% CI 1.43-4.62; p = 0.002). A nomogram including CTP, creatinine, and sodium measured at baseline accurately (concordance: 0.752) stratified the risk of death. CONCLUSION: The majority of 'non-high-risk' patients with AVB have an excellent prognosis, if treated according to current recommendations. However, about one-fifth of patients, i.e. those with CTP ≥8 and/or high creatinine levels or hyponatremia, have a considerable risk of death within 1 year of the index bleed. Future clinical trials should investigate whether elective TIPS placement reduces mortality in these patients. IMPACT AND IMPLICATIONS: Pre-emptive transjugular intrahepatic portosystemic shunt placement improves outcomes in high-risk acute variceal bleeding; nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation. This is the first large-scale study investigating prognostic factors for re-bleeding and mortality in 'non-high-risk' acute variceal bleeding. While no clinically meaningful predictors were identified for re-bleeding, we developed a nomogram integrating baseline Child-Turcotte-Pugh score, creatinine, and sodium to stratify mortality risk. Our study paves the way for future clinical trials evaluating whether elective transjugular intrahepatic portosystemic shunt placement improves outcomes in presumably 'non-high-risk' patients who are identified as being at increased risk of death.

Use of albumin infusion for cirrhosis-related complications: An international position statement.

Background & Aims: Numerous studies have evaluated the role of human albumin (HA) in managing various liver cirrhosis-related complications. However, their conclusions remain partially controversial, probably because HA was evaluated in different settings, including indications, patient characteristics, and dosage and duration of therapy. Methods: Thirty-three investigators from 19 countries with expertise in the management of liver cirrhosis-related complications were invited to organise an International Special Interest Group. A three-round Delphi consensus process was conducted to complete the international position statement on the use of HA for treatment of liver cirrhosis-related complications. Results: Twelve clinically significant position statements were proposed. Short-term infusion of HA should be recommended for the management of hepatorenal syndrome, large volume paracentesis, and spontaneous bacterial peritonitis in liver cirrhosis. Its effects on the prevention or treatment of other liver cirrhosis-related complications should be further elucidated. Long-term HA administration can be considered in specific settings. Pulmonary oedema should be closely monitored as a potential adverse effect in cirrhotic patients receiving HA infusion. Conclusions: Based on the currently available evidence, the international position statement suggests the potential benefits of HA for the management of multiple liver cirrhosis-related complications and summarises its safety profile. However, its optimal timing and infusion strategy remain to be further elucidated. Impact and implications: Thirty-three investigators from 19 countries proposed 12 position statements on the use of human albumin (HA) infusion in liver cirrhosis-related complications. Based on current evidence, short-term HA infusion should be recommended for the management of HRS, LVP, and SBP; whereas, long-term HA administration can be considered in the setting where budget and logistical issues can be resolved. However, pulmonary oedema should be closely monitored in cirrhotic patients who receive HA infusion.

Anticoagulation improves survival in patients with cirrhosis and portal vein thrombosis: The IMPORTAL competing-risk meta-analysis.

BACKGROUND & AIMS: Previous meta-analyses demonstrated the safety and efficacy of anticoagulation in the recanalization of portal vein thrombosis in patients with cirrhosis. Whether this benefit translates into improved survival is unknown. We conducted an individual patient data (IPD) meta-analysis to assess the effect of anticoagulation on all-cause mortality in patients with cirrhosis and portal vein thrombosis. METHODS: In this IPD meta-analysis, we selected studies comparing anticoagulation vs. no treatment in patients with cirrhosis and portal vein thrombosis from PubMed, Embase, and Cochrane databases (until June 2020) (PROSPERO no.: CRD42020140026). IPD were subsequently requested from authors. The primary outcome - the effect of anticoagulation on all-cause mortality - was assessed by a one-step meta-analysis based on a competing-risk model with liver transplantation as the competing event. The model was adjusted for clinically relevant confounders. A multilevel mixed-effects logistic regression model was used to determine the effect of anticoagulation on recanalization. RESULTS: Individual data on 500 patients from five studies were included; 205 (41%) received anticoagulation and 295 did not. Anticoagulation reduced all-cause mortality (adjusted subdistribution hazard ratio 0.59; 95% CI 0.49-0.70), independently of thrombosis severity and recanalization. The effect of anticoagulation on all-cause mortality was consistent with a reduction in liver-related mortality. The recanalization rate was higher in the anticoagulation arm (adjusted odds ratio 3.45; 95% CI 2.22-5.36). The non-portal-hypertension-related bleeding rate was significantly greater in the anticoagulation group. CONCLUSIONS: Anticoagulation reduces all-cause mortality in patients with cirrhosis and portal vein thrombosis independently of recanalization, but at the expense of increasing non-portal hypertension-related bleeding. PROSPERO REGISTRATION NUMBER: CRD42020140026. IMPACT AND IMPLICATIONS: Anticoagulation is effective in promoting recanalization of portal vein thrombosis in patients with cirrhosis, but whether this benefit translates into improved survival is controversial. Our individual patient data meta-analysis based on a competing-risk model with liver transplantation as the competing event shows that anticoagulation reduces all-cause mortality in patients with cirrhosis and portal vein thrombosis independently of recanalization. According to our findings, portal vein thrombosis may identify a group of patients with cirrhosis that benefit from long-term anticoagulation.

Direct peroral cholangioscopy with conventional upper gastrointestinal endoscope.

An 83-year-old male with a history of Whipple procedure (pancreatoduodenectomy) due to pancreatic cancer, underwent endoscopic retrograde colangiopancreatography (ERCP) for acute cholangitis. Because of the altered anatomy, an upper gastrointestinal endoscope was used. Severe stricture of the hepaticojejunal anastomosis was found. The anastomotic stricture was dilated with a 12mm through-the-scope (TTS) balloon under fluoroscopy and direct visualization. Right and left ducts were explored with Dormia basket and balloon, with extraction of bile duct stones and pus. Cholangioscopy with upper gastrointestinal endoscope was performed and residual cholesterol stones were identified in branches of the left hepatic duct and these were removed with the stone extraction balloon under endoscopic visualization. Ciprofloxacin was administered for 5 days and post interventional course was uneventful. Direct peroral colangioscopy using a conventional endoscope provides high quality endoscopic imaging, enabling access to virtual chromoendoscopy and the 2.8 mm diameter working channel allows for interventional procedures. This strategy is useful and economical, helping confirm clearance of common bile duct stones, while allowing extraction of any residual stones. New, cost effective scopes for peroral cholangioscopy are needed to improve the safety and success rate.

Refractory benign esophageal strictures - Cut or dilate?

A 67-year-old male patient with long term gastroesophageal reflux disease (GERD) on double dose proton pump inhibitors, presented with dysphagia for soft foods. He underwent upper gastrointestinal (UGI) endoscopy which revealed a severe regular stricture at the level of the esophagogastric junction with a residual luminal orifice measuring 2 mm. Biopsies at the site of the stricture ruled out malignancy and were suggestive of peptic etiology. The patient underwent twelve endoscopic dilatation sessions, 11 of them with Savary-Guillard bougies and 1 with TTS balloon, up to a maximal diameter of 18 mm, with only partial relief of dysphagia symptoms. Due to the persistence of the stricture and dysphagia symptoms, incisional therapy was performed in two endoscopic sessions at the site of the stricture was performed with a Mori´s knife parallel to the longitudinal axis of the esophagus in a radial manner in all of the quadrants. There were no adverse events. On follow-up, 2 months later after the last session, the patient had a significant improvement and did not have any dysphagia symptoms. UGI endoscopy revealed minimal residual narrowing at the site of the previous stricture in the distal esophagus. He remains asymptomatic after 6 months follow-up.

Detection and Characterization of Early Gastric Cancer.

In this review, we would like to focus on risk stratification and quality indicators of diagnostic upper gastrointestinal endoscopy in the detection and characterization of early gastric cancer. Preparation of the upper gastrointestinal tract with mucolytic agents or simethicone is often overlooked in the west, and this inexpensive step prior to endoscopy can greatly improve the quality of imaging of the upper digestive tract. Risk stratification based on epidemiological features including family history, Helicobacter pylori infection status, and tobacco smoking is often overlooked but may be useful to identify a subgroup of patients at higher risk of developing gastric cancer. Quality indicators of diagnostic upper gastrointestinal endoscopy are now well defined and include: minimal inspection time of 3 min, adequate photographic documentation of upper gastrointestinal landmarks, utilization of advanced endoscopic imaging technology including narrow band imaging and blue laser imaging to detect intestinal metaplasia and characterize early gastric cancer; and standardized biopsy protocols allow for histological evaluation of gastric mucosa and detection of atrophic gastritis and intestinal metaplasia. Finally, endoscopic and histologic classifications such as the Kimura-Takemoto Classification of atrophic gastritis and the OLGA-OLGIM classifications may help stratify patients at a higher risk of developing early gastric cancer.

Rebleeding and mortality risk are increased by ACLF but reduced by pre-emptive TIPS.

BACKGROUND & AIMS: The relationship between acute-on-chronic liver failure (ACLF) and acute variceal bleeding (AVB) is poorly understood. Specifically, the prevalence and prognosis of ACLF in the context of AVB is unclear, while the role of transjugular intrahepatic portosystemic shunt (TIPS) in the management in patients with ACLF has not been described to date. METHODS: A multicenter, international, observational study was conducted in 2,138 patients from 34 centers between 2011 and 2015. ACLF was defined and graded according to the EASL-CLIF consortium definition. Placement of pre-emptive TIPS (pTIPS) was based on individual center policy. Patients were followed-up for 1 year, until death or liver transplantation. Cox regression and competing risk models (Gray's test) were used to identify independent predictors of rebleeding or mortality. RESULTS: At admission, 380/2,138 (17.8%) patients had ACLF according to EASL-CLIF criteria (grade 1: 38.7%; grade 2: 39.2%; grade 3: 22.1%). The 42-day rebleeding (19% vs. 10%; p <0.001) and mortality (47% vs. 10%; p <0.001) rates were higher in patients with ACLF and increased with ACLF grades. Of note, the presence of ACLF was independently associated with rebleeding and mortality. pTIPS placement improved survival in patients with ACLF at 42 days and 1 year. This effect was also observed in propensity score matching analysis of 66 patients with ACLF, of whom 44 received pTIPs and 22 did not. CONCLUSIONS: This large multicenter international real-life study identified ACLF at admission as an independent predictor of rebleeding and mortality in patients with AVB. Moreover, pTIPS was associated with improved survival in patients with ACLF and AVB. LAY SUMMARY: Acute variceal bleeding is a deadly complication of liver cirrhosis that results from severe portal hypertension. This study demonstrates that the presence of acute-on-chronic liver failure (ACLF) is the strongest predictor of mortality in patients with acute variceal bleeding. Importantly, patients with ACLF and acute variceal (re)bleeding benefit from pre-emptive (early) placement of a transjugular intrahepatic portosystemic shunt.

Generalized peripheral lymphadenopathy in a patient treated for chronic HCV infection.

BACKGROUND: A 62-year-old white woman was admitted to hospital with a 2-month history of progressive, painless, left supraclavicular and axillary lymph node enlargement. The patient's history was significant for chronic HCV infection, for which she had just completed a 48-week course of treatment with pegylated interferon alpha (180 microg once weekly) plus ribavirin (1,000 mg daily). She attained an end-of-treatment response and subsequent qualitative measurement of HCV RNA confirmed a sustained virological response. The onset of progressive painless lymph node enlargement had been noted by the patient during the last 2 weeks of her treatment for HCV. INVESTIGATIONS: Physical examination, otorhinolaryngological examination, laboratory investigations (including complete blood counts, liver function tests and serological tests), mammography, thyroid and abdominal ultrasound, CT scans, abdominal MRI, upper gastrointestinal endoscopy, colonoscopy, supraclavicular lymph node biopsy, (67)Ga scintigraphy and bronchoalveolar lavage. DIAGNOSIS: Granulomatous lymphadenitis of uncertain etiology with sarcoid-type and tuberculoid-type granulomas. MANAGEMENT: Standard antituberculosis treatment with isoniazid, rifampicin, pyrazinamide and ethambutol for 2 months, followed by isoniazid and rifampicin for 7 months.