Long-term albumin administration in patients with cirrhosis and ascites: A meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Ascites is a common complication of cirrhosis, and it is associated with increased mortality. The aim of this study was to evaluate the efficacy of long-term albumin administration in decreasing mortality and other complications of patients with cirrhosis and ascites. METHODS: A systematic review was performed using MEDLINE and Embase databases. Randomized controlled trials evaluating long-term albumin administration in patients with cirrhosis and ascites were considered eligible, as long as at least one of the following outcomes was evaluated: mortality, recurrence of ascites/need for paracentesis, refractory ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, gastrointestinal bleeding, or adverse events. Meta-analysis was performed using the random-effects model, through the Mantel-Haenszel method. The study protocol was registered at PROSPERO platform (CRD42019130078). RESULTS: The literature search yielded 1517 references. Five randomized controlled trials fulfilled the selection criteria and were included in this meta-analysis, involving 716 individuals. Patients receiving long-term albumin had significantly lower risk of recurrence of ascites/need for paracentesis when compared with controls (risk ratio = 0.56, 95% confidence interval = 0.48-0.67, P < 0.00001). There was no evidence of significant difference between the long-term albumin and control groups regarding mortality, refractory ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, gastrointestinal bleeding, or adverse events. CONCLUSIONS: Long-term albumin administration in patients with cirrhosis and ascites decreases recurrence of ascites/need for paracentesis. At this point, there is no evidence of significant benefits of long-term albumin administration regarding mortality or other complications of cirrhosis.

Hepatorenal syndrome: Current concepts related to diagnosis and management.

 Renal failure in cirrhotic patients is a very severe condition. Hepatorenal syndrome has the worst prognosis among all causes of kidney failure in such patients. Hepatorenal syndrome is diagnosed especially in cirrhotic patients with ascites who develop loss renal function, despite diuretic suspension and volume expansion with albumin and for whom other causes of kidney injury have been excluded. Patients with hepatorenal syndrome should be treated with a vasoconstrictor in combination with albumin as a bridge to receiving a liver transplant. The vasoconstrictor of choice is terlipressin or noradrenaline. In spite of higher drug-related costs associated to terlipressin, initial evidence demonstrates that, considering all direct medical costs involved, the treatment strategy using terlipressin is probably more economical than that using noradrenaline.

Retrospective analysis of the efficacy and survival associated with cTACE and DEB-TACE in the palliative treatment of hepatocellular carcinoma: experience of a tertiary care hospital in southern Brazil.

Objective: To compare conventional transarterial chemoembolization (cTACE) and drug-eluting bead TACE (DEB-TACE) in terms of efficacy, survival, and adverse effects in patients with hepatocellular carcinoma who are not candidates for curative therapy. Materials and Methods: This was a retrospective study of patients with hepatocellular carcinoma who underwent cTACE or DEB-TACE for palliative treatment between January 2009 and December 2021. The Kaplan-Meier method was used for survival analysis. Values of p < 0.05 were considered statistically significant. Results: We evaluated 268 patients, of whom 70 underwent DEB-TACE and 198 underwent cTACE. There was no significant difference between the groups regarding sex, age, or etiology of cirrhosis. The proportion of patients achieving a complete response on imaging examinations was higher in the cTACE group (31.8% vs. 16.1%), whereas that of patients achieving a partial response was higher in the DEB-TACE group (33.9% vs.19.7%), and the differences were significant (p = 0.014). The mortality rate was similar between the groups. The survival rate in the DEB-TACE and cTACE groups, respectively, was 87.0% and 87.9% at one year, 35.1% and 32.9% at three years, and 20.5% and 18.1% at five years (p = 0.661). There was no significant difference between the DEB-TACE and cTACE groups in terms of the frequency of adverse events (7.1% vs. 17.8%; p = 0.052). The most common complication in both groups was post-embolization syndrome. Conclusion: Although a complete response was more common among the patients who underwent cTACE, there was no difference in survival between the groups and the frequency of adverse events was similar.

Objetivo: Comparar a eficácia, sobrevida e efeitos adversos entre cTACE e DEB-TACE em pacientes com carcinoma hepatocelular não candidatos a terapia curativa. Materiais e Métodos: Estudo retrospectivo de pacientes com carcinoma hepatocelular submetidos a cTACE ou DEB-TACE para tratamento paliativo entre janeiro de 2009 e dezembro de 2021. Foi utilizado o método Kaplan-Meier para análise de sobrevida. Valor de p < 0,05 foi considerado estatisticamente significante. Resultados: Foram avaliados 268 pacientes, dos quais 70 foram submetidos a DEB-TACE e 198 foram submetidos a cTACE. Não houve diferença em relação ao sexo, idade e etiologia da cirrose. O grupo cTACE apresentou maior porcentual de resposta completa em exames de imagem (31,8% vs. 16,1%) e o grupo DEB-TACE apresentou maior porcentual de resposta parcial (33,9% vs.19,7%), com valor de p = 0,014. A mortalidade foi semelhante. As taxas de sobrevivência para os grupos DEB-TACE e cTACE foram 87,0% e 87,9% em um ano, 35,1% e 32,9% em três anos e 20,5% e 18,1% em cinco anos, respectivamente (p = 0,661). Em relação à frequência de eventos adversos, não houve diferença significativa entre os grupos (7,1% na DEB-TACE vs. 17,8% na cTACE; p = 0,052). A complicação mais comum, em ambos os grupos, foi a síndrome pós-embolização. Conclusão: Embora tenha sido observada maior frequência de resposta completa em pacientes submetidos a cTACE, não houve diferença na sobrevida dos pacientes entre os grupos. A taxa de eventos adversos também foi semelhante.

The effect of celecoxib on the development of diethylnitrosamine-induced liver tumors in rats.

BACKGROUND/AIMS: Hepatocellular carcinoma is one of the most commonly diagnosed malignant tumors in the world, and it typically has a poor prognosis. Extensive studies have examined the effects of non-steroidal anti-inflammatory drugs selective to COX-2 on the chemoprevention of various tumors. The objective of this study is to observe the effect of celecoxib on the development of liver tumors in rats. MATERIAL AND METHODS: Hepatocellular carcinoma was induced in a group of 75 rats with the carcinogen diethylnitrosamine. The animals were divided into 5 groups. Three groups received various doses of celecoxib, one group received indomethacin, and a control group received no non-steroidal selective anti inflammatory drugs. RESULTS: The experimental model was considered to be successful because 78% of the rats in the control group developed liver tumors. The number of neoplastic lesions was similar among the celecoxib, indomethacin and control groups, although the nodule diameter of the lesions was smaller in the celecoxib group. Better results were observed in animals that received celecoxib at doses of 6 and 9 mg/kg/ day; 4 rats in these groups did not show any neoplastic histological lesions, and a greater proportion of the nodules in the other animals in these groups were benign than in the groups that did not use celecoxib. CONCLUSIONS: These results suggest that celecoxib may play a role in modifying the natural history of hepatocellular carcinoma development.

Results of transarterial chemoembolization of hepatocellular carcinoma as a bridging therapy to liver transplantation.

Objective: To evaluate the degree of tumor necrosis after transarterial chemoembolization (TACE), used as a bridging therapy in patients awaiting liver transplantation, and its effect on survival. Materials and Methods: This was a retrospective cohort study involving 118 patients submitted to TACE prior to liver transplantation, after which the degree of tumor necrosis in the explant and post-transplant survival were evaluated. Results: Total necrosis of the neoplastic nodule in the explant was observed in 76 patients (64.4%). Of the patients with total necrosis in the explanted liver, 77.8% had presented a complete response on imaging examinations. Drug-eluting bead TACE (DEB-TACE), despite showing a lower rate of complications than conventional TACE, provided a lower degree of total necrosis, although there was no statistical difference between the two. By the end of the study period, 26 of the patients had died. Survival was longer among the patients with total necrosis than among those with partial or no necrosis (HR = 2.24 [95% CI: 0.91-5.53]; p = 0.078). Conclusion: In patients undergoing TACE as a bridging therapy, total tumor necrosis appears to be associated with improved patient survival.

Objetivo: Avaliar os resultados da necrose tumoral após quimioembolização transarterial (TACE) como terapia ponte e seu reflexo na sobrevida dos pacientes. Materiais e Métodos: Estudo de coorte retrospectivo, com 118 pacientes que realizaram TACE, em que foram avaliados o grau de necrose tumoral no explante e a sobrevida pós-transplante. Resultados: Necrose total do nódulo neoplásico no explante foi observada em 76 pacientes (64,4%). Observou-se que 77,8% dos pacientes com necrose total no explante hepático tinham apresentado resposta completa nos exames de imagem. A DEB-TACE, apesar de ter demonstrado menor taxa de intercorrências, proporcionou menor grau de necrose total em relação à TACE convencional, a despeito de não haver diferença estatística. Ao final do seguimento do estudo, o número de óbitos foi de 26. A sobrevida foi maior nos pacientes que tiveram necrose total quando comparada com grau de necrose parcial ou ausência de necrose [HR = 2,24 (IC 95%: 0,91-5,53); p = 0,078]. Conclusão: Necrose completa do tumor nos pacientes submetidos a TACE como terapia ponte parece estar associada com melhora da sobrevida.

Evaluation of the C3435T polymorphism in the MDR1 gene in patients with hepatocellular carcinoma.

INTRODUCTION: Considering the high prevalence of liver tumors and the impact on patient survival, a greater understanding of the biological behavior of those tumors if of great importance. The multidrug resistance gene (MDR1) may present as single nucleotide polymorphism (SNP) which can affect the expression and activity of P-glycoprotein (Pgp), and high expression of Pgp has been associated with a worse prognosis in affected patients. OBJECTIVE: To correlate the C3435T polymorphism in the MDR1 gene with the immunohistochemical expression of Pgp. MATERIAL AND METHODS: A total of 67 samples from patients with diagnosis of hepatocellular carcinoma (HCC), collected in the period from 2000 to 2009, were analyzed. The polymorphism in the MDR1 gene was determined by the technique of allele-specific real time PCR using TaqMan assay, and the expression of protein Pgp was evaluated by immunohistochemistry. RESULTS: Among the samples evaluated, 56 (83.6%) were from male patients and 11 (16.4%) from females. Mean age was 60.6 years (± 8.8), ranging from 37 to 85 years. The etiology of the HCC was related to hepatitis C virus infection (HCV) in 31 (46.3%) of cases, followed by hepatitis C virus infection + alcohol in 24 cases (35.8%), alcohol in 4 cases (6)%, hepatitis B virus (HBV) in 4 cases (6%) and other factors in 4 cases (6%). Liver transplantation was performed in 48 cases (71.6%) and hepatectomia in 19 cases (28.4%). The genotypes CC, CT and TT showed frequencies of 25.4%, 41.8% and 32.8%, respectively, and the allele frequencies were 46.3% for allele C and 53.7% for allele T. The expression of Pgp in over 75% of the cells was significantly more frequent in tumor tissue. On the other hand, a low expression of Pgp, in less than 25% of the cells, was significantly more frequent in non-tumor tissue. The Pgp expression in more than 50% of tumor cells of individuals with genotypes CC, CT and TT was 15.7%, 51.0% and 33.3%, respectively, and was significantly higher when in the presence of allele T (p = 0.002). CONCLUSION: The presence of the polymorphic allele T is related to increased expression of Pgp protein in patients with HCC.

Albumin administration in patients with cirrhosis: Current role and novel perspectives.

Mortality in cirrhosis is mostly associated with the development of clinical decompensation, characterized by ascites, hepatic encephalopathy, variceal bleeding, or jaundice. Therefore, it is important to prevent and manage such complications. Traditionally, the pathophysiology of decompensated cirrhosis was explained by the peripheral arterial vasodilation hypothesis, but it is currently understood that decompensation might also be driven by a systemic inflammatory state (the systemic inflammation hypothesis). Considering its oncotic and nononcotic properties, albumin has been thoroughly evaluated in the prevention and management of several of these decompensating events. There are formal evidence-based recommendations from international medical societies proposing that albumin be administered in individuals with cirrhosis undergoing large-volume paracentesis, patients with spontaneous bacterial peritonitis, those with acute kidney injury (even before the etiological diagnosis), and those with hepatorenal syndrome. Moreover, there are a few randomized controlled trials and meta-analyses suggesting a possible role for albumin infusion in patients with cirrhosis and ascites (long-term albumin administration), individuals with hepatic encephalopathy, and those with acute-on-chronic liver failure undergoing modest-volume paracentesis. Further studies are necessary to elucidate whether albumin administration also benefits patients with cirrhosis and other complications, such as individuals with extraperitoneal infections, those hospitalized with decompensated cirrhosis and hypoalbuminemia, and patients with hyponatremia.

Acute hepatitis C in Brazil: results of a national survey.

The incidence of acute hepatitis C has decreased in the world. However, new cases are still reported. The objective of this study was to obtain data of acute hepatitis C in Brazil and to identify risk factors of transmission, diagnostic criteria, clinical presentation, evolution, and treatment. A questionnaire was sent to all members of the Brazilian Society of Hepatology. Sixteen centers participated with a total of 170 cases between 2000 and 2008. Among them, 37 had chronic renal failure on hemodialysis and were evaluated separately. The main diagnostic criterion in non-uremic patients was ALT (alanine aminotransferase) elevation associated with risk factors. In patients with chronic renal failure, anti-hepatitis C virus (HCV) seroconversion was the most frequent criterion. Among the 133 non-uremic patients the main risk factors were hospital procedures, whereas in hemodialysis patients, dialysis was the single risk factor in 95% of the cases. Jaundice was more frequent in non-uremic patients (82% vs. 13%; P < 0.001) and ALT levels were higher in these individuals (P < 0.001). Spontaneous clearance was more frequent in non-uremic patients (51% vs. 3%; P < 0.001). Sixty-five patients were treated: 39 non-uremic patients and 26 on dialysis. Sustained virological response rates were 60% for non-uremic and 58% for uremic patients (P = 0.98). There was no association of these rates with the study variables. These findings show that cases of acute hepatitis C are still occurring and have been related predominantly to hospital procedures. Measures to prevent nosocomial transmission should be adopted rigorously and followed to minimize this important source of infection observed in this survey.

Current impact of viral hepatitis on liver cancer development: The challenge remains.

Chronic infections due to hepatitis B and hepatitis C viruses are responsible for most cases of hepatocellular carcinoma (HCC) worldwide, and this association is likely to remain during the next decade. Moreover, viral hepatitis-related HCC imposes an important burden on public health in terms of disability-adjusted life years. In order to reduce such a burden, some major challenges must be faced. Universal vaccination against hepatitis B virus, especially in the neonatal period, is probably the most relevant primary preventive measure against the development of HCC. Moreover, considering the large adult population already infected with hepatitis B and C viruses, it is also imperative to identify these individuals to ensure their access to treatment. Both hepatitis B and C currently have highly effective therapies, which are able to diminish the risk of development of liver cancer. Finally, it is essential for individuals at high-risk of HCC to be included in surveillance programs, so that tumors are detected at an early stage. Patients with hepatitis B or C and advanced liver fibrosis or cirrhosis benefit from being followed in a surveillance program. As hepatitis B virus is oncogenic and capable of leading to liver cancer even in individuals with early stages of liver fibrosis, other high-risk groups of patients with hepatitis B are also candidates for surveillance. Considerable effort is required concerning these strategies in order to decrease the incidence and the mortality of viral hepatitis-related HCC.

Hepatotoxicity due to rifampicin, isoniazid and pyrazinamide in patients with tuberculosis: is anti-HCV a risk factor?

BACKGROUND AND RATIONALE: Among the adverse events related to tuberculosis treatment, hepatotoxicity is the most serious, and recognition of risk factors for it is essential to achieve successful therapy. The aim of the study is to evaluate the role of anti-HCV as a risk factor for hepatotoxicity in hospitalized patients under tuberculosis treatment with rifampicin, isoniazid and pyrazinamide (RHZ). METHODS: Historical cohort study carried out at Hospital Sanatório Partenon, from 1998 to 2006. Patients aged 18 years or older, tested for anti-HCV, who presented normal pre-treatment aminotransferases (AST, ALT) and bilirrubin and who used RHZ during hospitalization were included in the study. Individuals who used anti-tuberculosis drugs six months prior to hospitalization, had clinical evidence of chronic liver disease or showed previous history of hepatotoxicity to RHZ were excluded. RESULTS: A sample of 534 patients was studied. The incidence of hepatotoxicity was 8.8% (n = 47). After univariate analysis, the following variables were associated to hepatotoxicity: anti-HIV positive, anti-HCV positive, use of antiretroviral therapy and high doses of rifampicin and isoniazid per kg of body weight (p < 0.05). When Cox regression was performed, anti-HIV positive [RR = 2.3 (IC(95% )1.2-4.1); p = 0.008] and high doses of isoniazid per kg of body weight [RR = 1.3 (IC(95%) 1.1-1.7); p = 0.016] remained independently associated to development of hepatotoxicity. CONCLUSIONS: In conclusion, the anti-HIV positive and high doses of isoniazid were considered independent risk factors for hepatotoxicity due to RHZ esqueme in the present study. Though univariate analysis showed that anti-HCV was associated to the outcome, it was not identified as an independent risk factor for hepatotoxicity related to the use of RHZ when the analysis was controlled to HIV.