Position paper on perioperative management and surgical risk in the patient with cirrhosis.

INTRODUCTION: Management of the patient with cirrhosis of the liver that requires surgical treatment has been relatively unexplored. In Mexico, there is currently no formal stance or expert recommendations to guide clinical decision-making in this context. AIMS: The present position paper reviews the existing evidence on risks, prognoses, precautions, special care, and specific management or procedures for patients with cirrhosis that require surgical interventions or invasive procedures. Our aim is to provide recommendations by an expert panel, based on the best published evidence, and consequently ensure timely, quality, efficient, and low-risk care for this specific group of patients. RESULTS: Twenty-seven recommendations were developed that address preoperative considerations, intraoperative settings, and postoperative follow-up and care. CONCLUSIONS: The assessment and care of patients with cirrhosis that require major surgical or invasive procedures should be overseen by a multidisciplinary team that includes the anesthesiologist, hepatologist, gastroenterologist, and clinical nutritionist. With respect to decompensated patients, a nephrology specialist may be required, given that kidney function is also a parameter involved in the prognosis of these patients.

New concepts in liver cirrhosis: clinical significance of sarcopenia in cirrhotic patients.

The natural history of cirrhotic patients is highly variable due to several factors including hepatic synthetic function, presence and degree of portal hypertension, the cause of cirrhosis, the possibility of resolution of the underlying damaging process, and the occurrence of liver cancer. Currently, D'Amico stage classification and Child-Pugh and Model for End-Stage Liver Disease (MELD) scores constitute the best tools to predict mortality in patients with cirrhosis; however, one of their main limitations is the lack of evaluation of the nutritional and functional status. Most widely recognized complications in cirrhotic patients include ascites, hepatic encephalopathy, variceal bleeding, kidney dysfunction, and hepatocellular carcinoma; however, sarcopenia or severe muscle wasting is one of the most common and frequently hidden complications which negatively impact survival, quality of life, and response to stressor, such as infection and surgery. In this review, we discuss the current accepted and new methods to evaluate prognosis in cirrhosis, and also analyze the current knowledge regarding incidence and clinical impact of malnutrition and sarcopenia in cirrhosis and their impact after liver transplantation. We also discuss existing and potential novel therapeutic strategies for malnutrition in cirrhosis, emphasizing the recognition of sarcopenia in cirrhosis in an effort to improve survival and reduced morbidity related to cirrhosis. Finally, we propose that future studies including sarcopenia with the MELD score may allow better prediction of mortality among cirrhotic patients waiting for liver transplantation; however, due to the worldwide shortage of organs for transplants, one of the vital clinical questions is the feasibility to treat sarcopenia in cirrhosis without the need of liver transplant.

Evaluation and management of emergencies in the patient with cirrhosis.

The approach to and management of critically ill patients is one of the most versatile themes in emergency medicine. Patients with cirrhosis of the liver have characteristics that are inherent to their disease that can condition modification in acute emergency treatment. Pathophysiologic changes that occur in cirrhosis merit the implementation of an analysis as to whether the overall management of a critically ill patient can generally be applied to patients with cirrhosis of the liver or if they should be treated in a special manner. Through a review of the medical literature, the available information was examined, and the evidence found on the special management required by those patients was narratively synthesized, selecting the most representative decompensations within chronic disease that require emergency treatment.

Cyclosporine A protects against primary biliary cirrhosis recurrence after liver transplantation.

Primary biliary cirrhosis (PBC) reoccurs in a proportion of patients following liver transplantation (LT). The aims of our study were to evaluate the risk factors associated with PBC recurrence and determine whether recurrent disease constitutes a negative predictor for survival. One hundred and eight patients receiving LT for end-stage PBC were studied. Recurrent disease was diagnosed in 28 patients (26%). Probability of recurrent PBC at 5 years was 13% and 29% at 10 years with an overall incidence of 3.97 cases per 100 patient years. By univariate Cox analysis use of tacrolimus (HR 6.28, 95% CI, 2.44-16.11, p < 0.001) and mycophenolate mofetil (HR 5.21, 95% CI, 1.89-14.33, p = 0.001) were associated with higher risk of recurrence; whereas use of cyclosporine A (CsA) and azathioprine were associated with reduced risk of recurrence (HR 0.13, 95% CI 0.05-0.35, p < 0.001 and HR 0.27, 95% CI 0.11-0.64, p = 0.003, respectively). In the multivariate Cox analysis, only CsA was independently associated with protection against recurrence (HR 0.17, 95% CI 0.06-0.71, p = 0.02). Five-year probability of survival was 83% and 96%, in patients without and with recurrence (log-rank test, p = 0.3). Although PBC transplant recipients receiving CsA have a lower risk of disease recurrence, the development of recurrent PBC did not impact on long-term patient survival.

Gastric capacity is related to body mass index in obese patients. A study using the water load test.

BACKGROUND: The role of gastrointestinal function in obesity is unknown. Recent studies have shown that satiety in obese patients is influenced by an abnormal gastric capacity. AIM: An easy and non-invasive tool, the water load test (WLT) was used to evaluate gastric capacity and how it relates to body mass index (BMI) in obese patients. METHODS: The WLT was performed in 32 patients with high BMI and 12 healthy volunteers. Water was ingested at a 15 mL/min rate. The maximal tolerable volume (MTV) was defined as the total ingested volume when patients stopped the test. RESULTS: A BMI > 30 was significantly associated with higher water consumption (2339 ± 306 mL) compared to controls (1830 ± 240 mL, p = 0.001). The MTV had a positive correlation with BMI (r = 0.68, p = 0.001). CONCLUSIONS: Obese subjects have an increased gastric capacity, as measured with the WLT. This greater drinking capacity has a positive correlation with the subjects' BMI.

[Effect of the administration of rectal indomethacin on amylase serum levels after endoscopic retrograde cholangiopancreatography, and its impact on the development of secondary pancreatitis episodes]. / Efecto de la administración de indometacina rectal sobre los niveles séricos de amilasa posteriores a colangiopancreatografía retrógrada endoscópica y su impacto en la aparición de episodios de pancreatitis secundaria.

BACKGROUND: Hyperamylasemia and acute pancreatitis represent the most frequent major complication after endoscopic retrograde cholangiopancreatography (ERCP), developing in 1-30% of cases. OBJECTIVE: To determine the incidence of hyperamylasemia and acute pancreatitis after ERCP, and to assess the utility of rectal indomethacin to prevent these events. MATERIAL AND METHODS: A randomized clinical trial. During a 12-month period 150 patients were included. They were divided up into a study group (n = 75), where 100 mg of rectal indomethacin were administered 2 hours prior to the procedure, and a control group (n = 75), which received rectal glycerin. Two hours after ERCP serum amylase levels were measured and classified as follows: 0or=600 IU/L. Clinical pancreatitis episodes were quantified and classified according to Ranson's criteria. RESULTS: Gender distribution: 100 women and 50 men. Mean age: 55.37 +/- 18.0 for the study group, and 51.1 +/- 17.0 for the control group. A diagnosis of benign pathology was present in 56 (74.7%) cases in the study group, and 59 (78.7%) controls. After ERCP 13 (17.3%) patients in the study group and 28 (37.3%) in the control group developed hyperamylasemia (p (2) 0.05). Hyperamylasemia > 600 IU/L was found in 3 patients in the study group, and in 10 in the control group (p = 0.001). Mild pancreatitis was detected in 4 (5.3%) patients in the study group, and in 12 (16%) patients in the control group (p = 0.034). There were no deaths or adverse drug reactions. CONCLUSIONS: Rectal indomethacin before ERCP decreases the risk of hyperamylasemia and pancreatitis. Indomethacine is a feasible, low-cost drug with minimal or nil side effects.

Systematic review: recurrent autoimmune liver diseases after liver transplantation.

BACKGROUND: Autoimmune liver diseases (AILD) constitute the third most common indication for liver transplantation (LT) worldwide. Outcomes post LT are generally good but recurrent disease is frequently observed. AIMS: To describe the frequency and risk factors associated with recurrent AILD post-LT and provide recommendations to reduce the incidence of recurrence based on levels of evidence. METHODS: A systematic review was performed for full-text papers published in English-language journals, using the keywords 'autoimmune hepatitis (AIH)', 'primary biliary cholangitis and/or cirrhosis (PBC)', 'primary sclerosing cholangitis (PSC)', 'liver transplantation' and 'recurrent disease'. Management strategies to reduce recurrence after LT were classified according to grade and level of evidence. RESULTS: Survival rates post-LT are approximately 90% and 70% at 1 and 5 years and recurrent disease occurs in a range of 10-50% of patients with AILD. Recurrent AIH is associated with elevated liver enzymes and IgG before LT, lymphoplasmacytic infiltrates in the explants and lack of steroids after LT (Grade B). Tacrolimus use is associated with increased risk; use of ciclosporin and preventive ursodeoxycholic acid with reduced risk of PBC recurrence (all Grade B). Intact colon, active ulcerative colitis and early cholestasis are associated with recurrent PSC (Grade B). CONCLUSIONS: Recommendations based on grade A level of evidence are lacking. The need for further study and management includes active immunosuppression before liver transplantation and steroid use after liver transplantation in autoimmune hepatitis; selective immunosuppression with ciclosporin and preventive ursodeoxycholic acid treatment for primary biliary cholangitis; and improved control of inflammatory bowel disease or even colectomy in primary sclerosing cholangitis.

[Predictive factors for portal hypertension in patients with primary sclerosing cholangitis]. / Factores predictores de hipertensión portal en los enfermos con colangitis esclerosante primaria.

BACKGROUND: Primary sclerosing cholangitis (PSC) is characterized by progressive destruction of bile ducts, which may lead to cirrhosis and portal hypertension. The factors associated with the presence of esophageal varices (EV) and the risk of bleeding have not been well defined. AIM: To determine the factors associated with the presence of EV and risk of bleeding in a cohort of patients with PSC. MATERIAL AND METHODS: We analyzed the demographic, biochemical and endoscopic characteristics, and follow-up of 32 patients with a diagnosis of PSC. All patients underwent endoscopic evaluation to determine the presence of EV at diagnosis and annually during follow-up. RESULTS: There were 24 men (75%) and 8 women (25%). The mean age was 40.2 years (range, 19-66). At diagnosis, none of the patients had a previous history of variceal bleeding and 4 (13%) had EV on endoscopic examination. In bivariate analysis, the factors associated with the presence of EV were: splenomegaly (4/6 vs 0/26; p < 0.001), ascites (2/4 vs 0/24; p < 0.001), thrombocytopenia (96 +/- 27 vs 299 +/- 135 x 10(3), p < 0.001), and hypoalbuminemia (2.4 +/- 0.6 vs 3.5 +/- 0.6 g/dl; p = 0.005). During a mean follow-up period of 7 years (range, 2-15 years), 6 patients developed EV and 7 patients had at least one episode of variceal bleeding. In logistic regression analysis, the factors independently associated with the presence of EV at diagnosis were thrombocytopenia (p = 0.001) and splenomegaly (p = 0.01). The factors associated with variceal bleeding were worsening of liver function (p = 0.01) and splenomegaly (p = 0.02). CONCLUSIONS: There are noninvasive indicators of portal hypertension that could predict the presence of EV and risk of bleeding in patients with PSC. The presence of thrombocytopenia, splenomegaly or worsening of liver function should be detected in these patients, as they could benefit from endoscopic surveillance.

[Seropositivity for Chlamydia pneumoniae in patients with primary biliary cirrhosis]. / Seropositividad para Chlamydia pneumoniae en pacientes con cirrosis biliar primaria.

INTRODUCTION: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by inflammatory injury and bile duct destruction. Recent studies suggest that Chlamydia pneumoniae could be associated with the development of PBC. The aim of this study was to determine the seroprevalence of C. pneumoniae in a cohort of patients with PBC. PATIENTS AND METHODS: The presence of IgG antibodies against C. pneumoniae was investigated in 46 patients with PBC and in 105 subjects without cirrhosis. RESULTS: Twenty-one patients (46%) with PBC had antibodies against C. pneumoniae compared with 74 subjects (71%) in the control group (OR = 0.6; 95% CI, 0.3-1.2; p = NS). Subanalysis of the PBC group showed that patients with C. pneumoniae antibodies had a higher frequency of advanced Child-Pugh stages (24% A, 52% B and 24% C vs 64% A, 32% B and 4% C; p = 0.01), a higher score on the Mayo Clinic Prognostic Index (7.8 +/- 2.1 vs 5.6 +/- 1.2; p = 0.004), a higher frequency of ascites (29% vs 4%; OR = 9.6; 95% CI, 1-87; p = 0.02), higher total bilirubin levels (4.5 +/- 2.5 mg/dl vs 2.4 +/- 4.3 mg/dl, p = 0.001) and lower serum albumin levels (2.6 +/- 0.9 g/dl vs 3.3 +/- 0.6 g/dl, p = 0.02). CONCLUSION: No association was found between C. pneumoniae infection and PBC in this study. An association was found between the severity of PBC and C. pneumoniae, which may suggest a deleterious effect of C. pneumoniae infection or a predisposition in advanced stages of PBC to acquire infection with this microorganism.

[Treatment modalities in patients with hepatocellular carcinoma: a retrospective series in a single institution in Mexico]. / Modalidades de tratamiento para pacientes con carcinoma hepatocelular: una serie retrospectiva de una sola institución en México.

BACKGROUND: To date, curative treatment options for hepatocellular carcinoma (HCC) include orthotopic liver transplantation or surgical resection. Most patients are detected with nonresectable or transplantable HCC due to disease extension or comorbid factors, and are therefore candidates for palliative treatments only. Few follow-up data are available in patients with HCC in Latin America. We therefore reviewed the experience of HCC treatment in a single institution over a 10-year period. PATIENTS AND METHOD: A total of 135 patients attending the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, a national referral center in Mexico, from January 1991 to December 2000 were included. In all patients etiology, stage, and diagnostic and therapeutic measures were documented. Survival time was calculated as a function of staging and therapy. RESULTS: Of 135 patients, 77 (57%) were men and 58 (43%) were women. The mean age at diagnosis was 59.17 years (range: 16-87 years). Cirrhosis was diagnosed in 89 patients (64.4%). The median overall survival for all patients with HCC was 7.9 months. Treatment included surgical resection (n=22), hepatic artery chemoembolization (n=10), percutaneous ethanol injection (n=6), systemic chemotherapy (n=5), tamoxifen (n=11), and thalidomide (n=1). Eighty patients received support measures. The median survival in the group of patients who underwent surgical resection (37.89 months) was significantly higher than that in the groups of patients who did not undergo resection. CONCLUSIONS: Patients with HCC who received no treatment had a median survival of 1.7 months. Hepatic resection offers the best chance of cure in patients with HCC. The strong association between HCC and cirrhotic liver disease makes surgical resection difficult in patients with low hepatic reserve.

[Pathogenesis of hepatitis C virus infection]. / Patogénesis de la infección por virus de hepatitis C.

The hepatitis C virus (HCV) is the leading cause of chronic liver disease worldwide. Chronic hepatitis C is a mayor cause of cirrhosis and hepatocellular carcinoma and HCV-related end-stage liver disease is, in many countries, the first cause of liver transplantation. HCV infection is characterized by its propensity to chronicity. Because of its high genetic variability, HCV has the capability to escape the immune response of the host. HCV is not directly cytopathic and liver lesions are mainly related to immune-mediated mechanisms that are characterized by a predominant type 1 helper cell response. Co-factor influencing the outcome of the disease including age, gender and alcohol consumption are poorly understood and other factors such as immunologic and genetic factors may play and important role. Recent studies have shown that the combination therapy with alpha interferon and ribavirin induces a sustained virological response in about 40% of patients with chronic hepatitis C. The lack of animal models and of in vitro cultures systems hampers the understanding of the pathogenesis of chronic hepatitis C and the development of new antivirals. The conjugation of polyethyleneglycol improved the pharmacodynamics and the efficacy of alpha interferon. The development of an effective vaccine remains the most difficult challenge. Because of the high protein variability of HCV, protective vaccines could be extremely difficult to produce and therapeutic vaccines seem more realistic. Considerable progress has been made in the field of HCV since its discovery 10 years ago but a major effort needs to be made in the next decade to control HCV-related disease.

Systematic review: managing suboptimal treatment responses in autoimmune hepatitis with conventional and nonstandard drugs.

BACKGROUND: Corticosteroid treatment for autoimmune hepatitis has been shown by randomised controlled clinical trials to ameliorate symptoms, normalise liver tests, improve histological findings and extend survival. Nevertheless, suboptimal responses to corticosteroid treatment still occur. AIM: To describe the current definitions, frequencies, clinical relevance and treatment options for suboptimal responses, and to discuss alternative medications that have been used off-label for these occurrences. METHODS: Literature search was made for full-text papers published in English using the keyword 'autoimmune hepatitis'. Authors' personal experience and investigational studies also helped to identify important contributions to the literature. RESULTS: Suboptimal responses to standard therapy include treatment failure (7%), incomplete response (14%), drug toxicity (13%) and relapse after drug withdrawal (50-86%). The probability of a suboptimal response prior to treatment is higher in young patients and in patients with a severe presentation, jaundice, high MELD score at diagnosis, multilobular necrosis or cirrhosis, antibodies to soluble liver antigen, or inability to improve by clinical indices within two weeks or by MELD score within 7 days of conventional corticosteroid treatment. Management strategies have been developed for the adverse responses and nonstandard drugs, including mycophenolate mofetil, budesonide, ciclosporin, tacrolimus, sirolimus and rituximab, are emerging as rescue therapies or alternative frontline agents. CONCLUSIONS: Once diagnosed, the suboptimal response should be treated by a highly individualised and well-monitored regimen, preferentially using first-line therapy. Nonstandard drugs warrant consideration as salvage or second-line therapies.

Rotterdam score predicts early mortality in Budd-Chiari syndrome, and surgical shunting prolongs transplant-free survival.

BACKGROUND: Budd-Chiari syndrome carries significant mortality, but factors predicting this outcome are uncertain. AIM: To determine factors associated with 3-month mortality and compare outcomes after surgical shunting or liver transplantation. METHODS: From 1985 to 2008, 51 patients with Budd-Chiari syndrome were identified. RESULTS: By logistic regression analysis, features associated with higher risk of 3-month mortality were Rotterdam class III, Clichy >6.6, model for end-stage liver disease (MELD) >20 and Child-Pugh C. Rotterdam class III had the best performance to discriminate 3-month mortality with sensitivity of 0.89 and specificity of 0.63, whereas Clichy >6.60 had sensitivity of 0.78 and specificity of 0.69; MELD >20 had sensitivity of 0.78 and specificity of 0.75 and Child-Pugh C had sensitivity of 0.67 and specificity of 0.72. Eighteen patients underwent surgical shunts and 14 received liver transplantation with no significant differences in survival (median survival 10 +/- 3 vs. 8 +/- 2 years; log-rank, P = 0.9). CONCLUSIONS: Rotterdam score is the best discrimination index for 3-month mortality in Budd-Chiari syndrome and should be used preferentially to determine treatment urgency. Surgical shunts constitute an important therapeutic modality that may help save liver grafts and prolong transplantation-free survival in a selected group of patients with Budd-Chiari syndrome.

Efecto de la administración de indometacina rectal sobre los niveles séricos de amilasa posteriores a colangiopancreatografía retrógrada endoscópica y su impacto en la aparición de episodios de pancreatitis secundaria / Effect of the rectal administration of indomethacin on amylase serum levels after endoscopic retrograde cholangiopancreatography, and its impact on the development of secondary pancreatitis episodes

Introducción: hiperamilasemia y pancreatitis aguda representan las complicaciones mayores más frecuentes posteriores a colangiopancreatografía retrógrada endoscópica (CPRE), apareciendo en 1-30% de los casos. Objetivo: determinar la incidencia de hiperamilasemia y pancreatitis posterior a CPRE y evaluar la utilidad de indometacina rectal para la prevención de estos. Material y métodos: ensayo clínico controlado. Durante un periodo de 12 meses se incluyeron 150 pacientes. Estos fueron divididos en grupo de estudio (n = 75), a quienes se administró indometacina rectal 100 mg 2 horas previas al procedimiento, y control (n = 75) que recibió glicerina. Dos horas posteriores a la CPRE se determinó el nivel de amilasa sérica y se clasificaron en: 0 = 600 UI/l. Los episodios de pancreatitis clínica se cuantificaron y clasificaron de acuerdo a los criterios de Ranson. Resultados: distribución por género: 100 mujeres y 50 hombres. Edad media: 55,37 ± 18,0 para el grupo de estudio y 51,1 ± 17,0 para el control. El diagnóstico de patología benigna se presentó en 56 (74,7%) casos del grupo de estudio y 59 (78,7%) del control. Posterior al procedimiento, 13 (17,3%) pacientes del grupo experimental y 28 (37,3%) del control desarrollaron hiperamilasemia (p 600 UI/l en 3 pacientes del grupo de estudio y 10 del control (p = 0,001). Se detectó pancreatitis leve en 5,3% de los pacientes del grupo de estudio y 16% del control (p < 0,05). No hubo mortalidad ni eventos adversos. Conclusiones: indometacina rectal previo a CPRE disminuye el riesgo de hiperamilasemia y pancreatitis. La indometacina es accesible, de bajo costo con mínimos o nulos efectos secundarios

Background: hyperamylasemia and acute pancreatitis represent the most frequent major complication after endoscopic retrograde cholangiopancreatography (ERCP), developing in 1-30% of cases. Objective: to determine the incidence of hyperamylasemia and acute pancreatitis after ERCP, and to assess the utility of rectal indomethacin to prevent these events. Material and methods: a randomized clinical trial. During a 12-month period 150 patients were included. They were divided up into a study group (n = 75), where 100 mg of rectal indomethacin were administered 2 hours prior to the procedure, and a control group (n = 75), which received rectal glycerin. Two hours after ERCP serum amylase levels were measured and classified as follows: 0 = 600 IU/L. Clinical pancreatitis episodes were quantified and classified according to Ranson’s criteria. Results: gender distribution: 100 women and 50 men. Mean age: 55.37 ± 18.0 for the study group, and 51.1 ± 17.0 for the control group. A diagnosis of benign pathology was present in 56 (74.7%) cases in the study group, and 59 (78.7%) controls. After ERCP 13 (17.3%) patients in the study group and 28 (37.3%) in the control group developed hyperamylasemia (p 600 IU/L was found in 3 patients in the study group, and in 10 in the control group (p = 0.001). Mild pancreatitis was detected in 4 (5.3%) patients in the study group, and in 12 (16%) patients in the control group (p = 0.034). There were no deaths or adverse drug reactions. Conclusions: rectal indomethacin before ERCP decreases the risk of hyperamylasemia and pancreatitis. Indomethacine is a feasible, low-cost drug with minimal or nil side effects