Response to Ursodeoxycholic Acid May Be Assessed Earlier to Allow Second-Line Therapy in Patients with Unresponsive Primary Biliary Cholangitis.

BACKGROUND: Response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) has been traditionally assessed 1 to 2 years after treatment initiation. With the development of new drugs, some patients may benefit from an earlier introduction of second-line therapies. AIMS: This study aims to identify whether well-validated response criteria could correctly identify individuals likely to benefit from add-on second-line therapy at 6 months. METHODS: Analysis of a multicenter retrospective cohort which included only patients with clear-cut PBC. RESULTS: 206 patients with PBC (96.6% women; mean age 54 ± 12 years) were included. Kappa concordance was substantial for Toronto (0.67), Rotterdam (0.65), Paris 1 (0.63) and 2 (0.63) criteria at 6 and 12 months, whereas Barcelona (0.47) and POISE trial (0.59) criteria exhibited moderate agreement. Non-response rates to UDCA was not statistically different when assessed either at 6 or 12 months using Toronto, Rotterdam or Paris 2 criteria. Those differences were even smaller or absent in those subjects with advanced PBC. Mean baseline alkaline phosphatase was 2.73 ± 1.95 times the upper limit of normal (× ULN) among responders versus 5.05 ± 3.08 × ULN in non-responders (p < 0.001). CONCLUSIONS: After 6 months of treatment with UDCA, the absence of response by different criteria could properly identify patients who could benefit from early addition of second-line therapies, especially in patients with advanced disease or high baseline liver enzymes levels.

Risk factors for cancer in patients with primary biliary cholangitis and autoimmune hepatitis and primary biliary cholangitis overlap syndrome.

INTRODUCTION AND OBJECTIVES: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) and PBC overlap syndrome (AIH/PBC) have been associated with a higher risk of hepatocellular carcinoma (HCC) and extra-hepatic malignancy (EHM). This study aims to assess potential risk factors associated with cancer development in PBC and AIH/PBC. MATERIALS AND METHODS: The Brazilian Cholestasis Study Group database was reviewed to compare clinical and laboratory features of PBC patients with HCC and EHM with those without cancer. RESULTS: Among the 752 PBC patients enrolled, 64 of them with AIH/PBC, 87 cancers were identified in 72 patients, including 20 cases of HCC and 67 of EHM. Patients with HCC had a higher prevalence of cirrhosis (95% vs. 32.5% of those subjects without cancer, p≤0.001), smoking (55% vs. 12.3%, p≤0.001), CREST syndrome (30% vs 7.6%, p=0.003) and prior azathioprine (30% vs 8%, p= 0.005) and prednisone (35% vs 14%, p= 0.018) use, whereas patients with EHM had a higher prevalence of smoking (42.3% vs 12.4% of those subjects without cancer, p= <0.001), AMA positivity (96.6% vs 80.1%, p≤0.001), azathioprine therapy (21% vs 7.9%, p= 0.01) and concurrent other autoimmune diseases. In multivariate analysis, cirrhosis, obesity and prior azathioprine therapy were independent risk factors for HCC, while Sjogren syndrome and psoriasis were associated with EHM. Fibrates reduced EHM risk. CONCLUSIONS: The prevalence of EHM is higher when compared to HCC in PBC patients. Cirrhosis, obesity, prior azathioprine use, and concurrent autoimmune diseases were significantly associated with cancer in PBC.

Visible intestinal peristalsis and chronic diarrhea due to a rare lymphoproliferative disease.

We present the case of a 45-year-old man with watery diarrhea for 2 years, leading to marked weight loss (52 kg). On admission, the patient presented with pallor, dehydration and cachexia. Abdominal examination revealed increased bowel sounds, painful and visible intestinal peristalsis, suggesting intestinal obstruction. There was no response to a gluten-free diet and nutritional support. Finally, the patient developed pulmonary infection, septic shock and died 3 months after admission. The diagnosis of CD4+/CD8+ indolent T-cell lymphoma of the GI tract was made post-mortem.

Anti-mitochondrial Antibody-Negative Primary Biliary Cholangitis Is Part of the Same Spectrum of Classical Primary Biliary Cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease in which anti-mitochondrial antibodies (AMA) are the diagnostic hallmark. Whether AMA-negative PBC patients represent a different phenotype of disease is highly debated. AIMS: The purpose of our study was to compare AMA-positive and AMA-negative PBC patients in a large non-white admixed Brazilian cohort. METHODS: The Brazilian Cholestasis Study Group multicentre database was reviewed to assess demographics, clinical features and treatment outcomes of Brazilian PBC patients, stratifying data according to AMA status. RESULTS: A total of 464 subjects (95.4% females, mean age 56 ± 5 years) with PBC were included. Three hundred and eighty-four (83%) subjects were AMA-positive, whereas 80 (17%) had AMA-negative PBC. Subjects with AMA-negative PBC were significantly younger (52.2 ± 14 vs. 59.6 ± 11 years, p = 0.001) and had their first symptom at an earlier age (43.2 ± 13 vs. 49.5 ± 12 years, p = 0.005). Frequency of type 2 diabetes was significantly increased in subjects with AMA-negative PBC (22.5% vs. 12.2%, p = 0.03). Lower IgM (272.2 ± 183 vs. 383.2 ± 378 mg/dL, p = 0.01) and triglycerides (107.6 ± 59.8 vs.129.3 ± 75.7 mg/dL, p = 0.025) and higher bilirubin (3.8 ± 13.5 vs. 1.8 ± 3.4 mg/dL, p = 0.02) levels were also observed in this subgroup. Response to ursodeoxycholic acid varied from 40.5 to 63.3% in AMA-positive and 34 to 62.3% in AMA-negative individuals, according to different response criteria. Outcomes such as development of liver-related complications, death and requirement for liver transplantation were similar in both groups. CONCLUSIONS: AMA-negative PBC patients are similar to their AMA-positive counterparts with subtle differences observed in clinical and laboratory features.

EncephalApp Stroop Test validation for the screening of minimal hepatic encephalopathy in Brazil.

INTRODUCTION AND OBJECTIVES: The EncephalApp Stroop Test was developed to more easily diagnose minimal hepatic encephalopathy (MHE). A cut-off of >274.9sec (ONtime+OFFtime) reached a 78% sensitivity and 90% specificity in the validation study, but it has been poorly studied in Brazil. We aim to analyze the usefulness of this diagnostic method and to describe a cut-off value to screen MHE in Brazil. METHODS: In this cross-sectional and single-center study, three positive psychometric tests defined the diagnosis of MHE as the gold standard. We evaluated gender, age, education, familiarity with smartphones, etiology of cirrhosis, Child-Pugh/MELD scores, and previous hepatic encephalopathy (HE). Healthy controls and patients without HE were compared for the task validation. The Chi-square and Mann-Whitney tests, logistic regression analysis, and ROC curves were used for statistical evaluation. RESULTS: We included 132 patients with cirrhosis (61% male) and 42 controls (62% male) around 51y. Sixty-three were diagnosed with MHE on psychometric tests and 23 had clinical HE. Viral hepatitis (38%) was the major etiology of cirrhosis. The median MELD was 10 and Child-Pugh A was more frequent (70%). There was no significant difference in test results between controls and patients without HE. There was also no influence of gender, age, education, and familiarity with smartphones in the test results. Child-Pugh A was associated with MHE (p=0.0106). A cut-off of >269.8sec (ONtime+OFFtime) had an 87% sensitivity and 77% specificity to detect MHE (p=0.002). CONCLUSION: This is a valid and reliable tool for screening MHE. However, optimal cut-off values need to be validated locally.

Non-Alcoholic Fatty Liver Disease in Long-Term Type 2 Diabetes: Role of rs738409 PNPLA3 and rs499765 FGF21 Polymorphisms and Serum Biomarkers.

Fibroblast growth factor 21 (FGF21) signaling and genetic factors are involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. However, these factors have rarely been studied in type 2 diabetes mellitus (T2D) patients from admixed populations such as in those of Brazil. Therefore, we aimed to evaluate rs738409 patanin-like phospholipase domain-containing protein (PNPLA3) and rs499765 FGF21 polymorphisms in T2D, and their association with NAFLD, liver fibrosis, and serum biomarkers (FGF21 and cytokeratin 18 levels). A total of 158 patients were included, and the frequency of NAFLD was 88.6%, which was independently associated with elevated body mass index. Significant liver fibrosis (≥F2) was detected by transient elastography (TE) in 26.8% of NAFLD patients, and was independently associated with obesity, low density lipoprotein, and gamma-glutamyl transferase (GGT). PNPLA3 GG genotype and GGT were independently associated with cirrhosis. PNPLA3 GG genotype patients had higher GGT and AST levels; PNPLA3 GG carriers had higher TE values than CG patients, and FGF21 CG genotype patients showed lower gamma-GT values than CC patients. No differences were found in serum values of FGF21 and CK18 in relation to the presence of NAFLD or liver fibrosis. The proportion of NAFLD patients with liver fibrosis was relevant in the present admixed T2D population, and was associated with PNPLA3 polymorphisms.

Changes in indications for outpatient percutaneous liver biopsy over 5 years: from hepatitis C to fatty liver disease.

INTRODUCTION: Although the use of non-invasive methods for assessment of liver fibrosis has reduced the need for biopsy, the diagnosis of liver damage still requires histological evaluation in many patients. We aim to describe the indications for percutaneous liver biopsy (PLB) and the rate of complications in an outpatient setting over 5 years. METHODS: This observational, single-center, and retrospective study included patients submitted to real-time ultrasound (US)-guided biopsies from 2015 to 2019. We collected age, gender, coagulation tests, comorbidities, and the number of needle passes. The association between the variables and complications was evaluated using the generalized estimating equations method. RESULTS: We analyzed 532 biopsies in 524 patients (55.3% male) with a median age of 49 years (range 13-74y). An average of 130.3 biopsies per year were performed in the first 3 years of the study versus 70.5 in the other 2y. The main indications were hepatitis C virus (HCV) infection (47.0%), autoimmune and cholestatic liver diseases (12.6%), and metabolic dysfunction-associated fatty liver disease (MAFLD) (12.1%). The number of HCV-related biopsies had a remarkable reduction, while MAFLD-related procedures have progressively raised over time. Around 54% of the patients reported pain, which was significantly associated with females (p=0.0143). Serious complications occurred in 11 patients (2.1%) and hospital admission was necessary in 10 cases (1.9%). No patient required surgical approach and there were no deaths. No significant association was found between the studied variables and biopsy-related complications. CONCLUSION: The indications for PLB in an outpatient setting have changed from HCV to MAFLD over the years. This procedure is safe and has a low rate of serious complications, but new strategies to prevent the pain are still needed, especially for females.

Cryptococcal peritonitis in patients on the liver transplant waitlist: Reporting two cases with opposite outcomes.

Cryptococcus neoformans is rarely associated with peritonitis in cirrhotic patients; nevertheless, it has a high mortality rate. Early diagnosis and prompt treatment may be the determining prognostic factors. This is a report of two patients awaiting a liver transplant who had opposite outcomes after the diagnosis of spontaneous cryptococcal peritonitis. In Patient 1, the fungal culture was positive in the blood and ascites. She had a poor evolution and died, which was likely caused by the delayed diagnosis and concomitant bacterial infections. In Patient 2, the fungus was found in the ascites, urine, and cerebrospinal fluid cultures. Antifungal treatment was effective. He underwent a liver transplant on the 83rd day of antifungal therapy and is still alive 1 year later. It is important to suspect fungal etiology when there is a lack of response to antibiotics in patients with decompensated cirrhosis and spontaneous peritonitis, and physicians must be aware of leukocyte count in the ascitic fluid, which is not so high in these cases. This report also emphasizes the need for the routine use of blood culture bottles for microbiological analysis of the ascitic fluid, as it was helpful to diagnose fungal peritonitis in both cases.

Massive iron overload and acute-on-chronic liver failure in a patient with Diamond-Blackfan anaemia: a case report.

BACKGROUND: Genetic anaemias lead us to reflect on the classic 'trolley dilemma', when there are two choices but neither one is satisfactory. Either we do not treat anaemia and the patient suffers from chronic tiredness and fatigue, or we do treat it through blood transfusions, leading to iron overload, which is a quite harmful consequence. CASE PRESENTATION: We present the case of a 34-year-old woman with Diamond-Blackfan anaemia (DBA). Bone marrow stem cell transplantation had not been accessible during her childhood, so she had been submitted to monthly blood transfusions throughout her life, leading to a hepatitis C virus infection (which was treated, achieving a sustained virological response when she was 18 years old), and secondary haemochromatosis. Despite chelation therapy, diffuse iron deposition was occurring in multiple organs, markedly in the heart and liver. Her serum ferritin was higher than 21,000 ng/mL and transferrin saturation reached 102%. When she faced heart decompensation, this congestive condition led to an acute liver injury overlapping pre-existing hepatic fibrosis. She progressed to haemodynamic and hepatic failure, with clinical features of acute-on-chronic liver failure (ACLF). Despite therapeutic optimisation, she died of respiratory insufficiency. An autopsy was performed and revealed the macroscopic and microscopic findings of a massive iron deposition in the liver, heart, lungs, spleen, bone marrow, thyroid and adrenal glands. We found marked advance of liver fibrosis (chronic damage), as well as necrosis of hepatocytes in zone 3 of the Rappaport acinus (acute damage), supporting the hypothesis of ACLF. The main feature responsible for acute liver decompensation seemed to be heart insufficiency. CONCLUSION: This is the first case reporting the sequence: DBA, multiple blood transfusions, secondary haemochromatosis, advanced liver fibrosis, heart failure, ACLF and death. A multidisciplinary team is essential to care for DBA patients, since there is a significant emotional burden related to the disease, which might impair an effective chelation therapy and lead to severe consequences due to iron deposition.

Vanishing bile duct syndrome related to DILI and Hodgkin lymphoma overlap: A rare and severe case.

Vanishing bile duct syndrome is a rare acquired condition, characterized by progressive loss of intrahepatic bile ducts leading to ductopenia and cholestasis. It can be associated with infections, ischemia, drug adverse reactions, neoplasms, autoimmune disease, and allograft rejection. Prognosis is variable and depends on the etiology of bile duct injury. We report the case of a 25-year-old female with cholestatic hepatitis and concomitant intakes of hepatotoxic substances, such as garcinia, field horsetail, and ketoprofen. On suspicion of a drug-induced liver injury, the drugs were promptly withdrawn and ursodeoxycholic acid was started with initial clinical and laboratory improvement, and the patient was discharged from the hospital. One month later, she had a new increase in bilirubin levels and canalicular enzymes, requiring a liver biopsy that showed significant loss of intrahepatic bile ducts, which was compatible with vanishing bile duct syndrome. This was confirmed by using cytokeratin 19 on immunohistochemistry. There was subsequent lymph node enlargement in several chains, and relevant weight loss. Histological analysis of a cervical lymph node revealed nodular sclerosis-subtype classic Hodgkin lymphoma. In this setting, vanishing bile duct syndrome was related to Hodgkin lymphoma and a drug-induced liver injury overlap, leading to progressive cholestasis with a worse prognosis. The patient's response to chemotherapy was poor, requiring biological therapy with brentuximab vedotin. It is crucial for physicians to create a broad differential diagnosis in suspected vanishing bile duct syndrome patients, especially to rule out malignancies.

Lysosomal Acid Lipase Deficiency Leading to Liver Cirrhosis: a Case Report of a Rare Variant Mutation.

Lysosomal acid lipase deficiency is a poorly diagnosed genetic disorder, leading to accumulation of cholesterol esters and triglycerides in the liver, with progression to chronic liver disease, dyslipidemia, and cardiovascular complications. Lack of awareness on diagnosis of this condition may hamper specific treatment, which consists on enzymatic replacement. It may prevent the progression of liver disease and its complications. We describe the case of a 53-year-old Brazilian man who was referred to our center due to the diagnosis of liver cirrhosis of unknown etiology. He was asymptomatic and had normal body mass index. He had dyslipidemia, and family history of myocardial infarction and stroke. Abdominal imaging tests showed liver cirrhosis features and the presence of intrahepatic calcifications. Initial investigation of the etiology of the liver disease was not elucidated, but liver biopsy showed microgoticular steatosis and cholesterol esters deposits in Kuppfer cells. The dosage of serum lysosomal acid lipase was undetectable and we found the presence of a rare homozygous mutation in the gene associated with the lysosomal acid lipase deficiency, (allele c.386A > G homozygous p.H129R).

Localized gastrointestinal amyloidosis presenting with protein-losing enteropathy and massive hemorrhage.

Amyloidosis of the gastrointestinal tract is usually a systemic disease. Localized gastrointestinal amyloidosis without evidence of extraintestinal involvement or an associated plasma cell dyscrasia is uncommon and does not usually cause death. We report a case of a patient with localized gastrointestinal amyloidosis who presented with protein-losing enteropathy and a fatal upper gastrointestinal bleed.

Epidemiology of HCC in Brazil: incidence and risk factors in a ten-year cohort.

BACKGROUND AND AIM: The lack of information about hepatocellular carcinoma (HCC) in Brazil weakens health policy in preventing deaths from the illness. The aim of this study was to establish the cumulative incidence and the risk factors for hepatocellular carcinoma development in patients under a surveillance program. MATERIAL AND METHODS: 884 patients with compensated cirrhosis were prospectively followed up for at least five years, from August 1998 until August 2008, with at least one annual ultrasonography liver examination and serum alpha fetoprotein (AFP) measurement. RESULTS: Among 884 patients, 72 (8.1%) developed a tumor with a median follow up of 21.4 months. In the hepatocellular carcinoma group, hepatitis C virus infection was the major etiological factor (65.3%), 56.9% (41/72) were male and the mean average age was 57 ± 10 years. The annual incidence of hepatocellular carcinoma was 2.9%. 79.2% (57/72) of HCCs were detected within Milan Criteria, and the mean survival time was 52.3 months, significantly higher than for those outside Milan, with a mean time of 40.6 months (p = 0.0003). CONCLUSION: The annual incidence of HCC among this large series of Brazilian cirrhotic patients was around 2.9% with a detection rate of 8.1%, or a cumulative incidence rate over five years of 14.3%. The three variables related to HCC risk were low serum albumin [HR: 0.518 (0.46-0.78)], high AFP > 20 ng/mL [HR: 3.16 (1.86-5.38)], and ethnicity (Brazilian-East Asian descendants vs. other mixed Brazilian ethnicities) [HR: 2.86 (1.48-5.53)].

Giant hepatic hemangioma in a patient with cirrhosis: challenging to manage.

Giant hepatic hemangiomas are occasional in patients with cirrhosis. It remains a challenge to decide on the need for treatment and choose the most appropriate intervention. A 62-year-old woman was recently diagnosed with cirrhosis and complained of upper abdominal fullness, reduction in oral food intake, and weight loss of 6 kg over the last three years. Upper digestive endoscopy evidenced thin-caliber esophageal varices and significant extrinsic compression of the lesser gastric curvature. Abdominal computed tomography revealed an exophytic tumor in the left hepatic lobe, measuring 11.5 cm, which had progressive centripetal contrast enhancement from the arterial phase, compatible with hepatic hemangioma. Serum tumor markers were negative, and her liver function was unimpaired. The patient underwent surgical resection (non-anatomical hepatectomy of segments II and III) which had no immediate complications, and the histopathological evaluation confirmed cavernous hepatic hemangioma. Two weeks later, she was admitted to the emergency room with jaundice, signs of hepatic encephalopathy, and moderate ascites, and was further diagnosed with secondary bacterial peritonitis. As no perforations, abscesses, or fistulas were observed on subsequent imaging tests, clinical management was successfully carried out. This case highlights that giant hepatic hemangiomas may be symptomatic and warrant treatment. In the setting of cirrhosis and portal hypertension, physicians should be aware of the risk of hepatic decompensation following surgical resection, even in patients with Child-Pugh class A.

Liver Transplantation After Previous Vena Cava Resection: Case Report.

In some specific cases, the surgical technique involved in liver transplantation can be challenging, as, for example, in cases of Budd-Chiari syndrome. This case describes a case of liver transplantation in a patient diagnosed with Budd-Chiari syndrome due to a previous surgery that required retrohepatic vena cava resection. During the liver transplantation procedure, a cavo-atrial anastomosis was performed through transdiaphragmatic access, with a good postoperative result, showing that, although challenging, this technique is a feasible option in specific cases.

Silent Destruction: Fulminant Hepatitis and the Hidden Danger of Weight Loss Drugs.

INTRODUCTION: The use of natural products for therapeutic purposes is a common practice throughout the world, in part, due to the global obesity epidemic and the search for products with appetite suppression and weight loss properties, which include nutritional supplements, vitamins and minerals to herbal products. It is known that such products may be associated with various adverse health effects. Thus, the objective of this study is to report a series of cases of patients, who presented fulminant liver failure (HFI) requiring liver transplantation (LT), related to the consumption of products used for weight loss. MATERIAL AND METHODS: This is a retrospective cohort based on the evaluation of patients listed for LT due to IHF at the Hospital das Clínicas of the Universidade Estadual de Campinas, between 1991 and 2022, with patients who had confirmed consumption of products with the aim of loss being selected. RESULTS: During the studied period, 92 patients were listed for HT due to IHF according to the Kings College criteria, with 5 cases being selected with proven consumption of herbal products for weight loss, and other causes that could explain the IHF were excluded. Four (80%) of the patients were female, with a mean age of 40.5 years, and 40% of the cases died. DISCUSSION AND CONCLUSIONS: Unlike traditional pharmaceutical medicines, in most countries, the commercialization of these products is not conditioned on clinical and safety evidence or prior approval by regulatory bodies. Hepatoxicity can be related to several factors, such as the presence of toxins naturally found in plants, the presence of heavy metals, contamination during obtaining or processing and the addition of substances omitted from the labels. The use of weight loss products can evolve with IHF, a fact that deserves attention, due to ease of access and growing demand, and it is important to regulate the trade of these products and raise public awareness about the risks of use without professional supervision and guidance.

Autoimmune hepatitis and primary biliary cholangitis overlap syndrome after COVID-19.

COVID-19 is commonly associated with high serum levels of pro-inflammatory cytokines, and the post-infection status can disturb self-tolerance and trigger autoimmune responses. We are reporting a 45-year-old male who was admitted with fatigue, jaundice, elevated liver enzymes (with cholestatic pattern), and acute kidney injury two weeks after recovering from a mild SARS-CoV-2 infection. Serologies for viral hepatitis and anti-mitochondrial antibody were negative, while anti-nuclear and anti-smooth muscle antibodies were positive. There were no signs of chronic liver disease, and a magnetic resonance cholangiography showed no dilatation of biliary ducts. Histologic evaluation of the liver evidenced numerous foci of lobular necrosis without ductopenia or portal biliary reaction. Considering the autoantibody profile and histologic changes, the medical team started oral prednisone, but there was a suboptimal biochemical response in the outpatient follow-up. Two months later, a second liver biopsy was performed and revealed non-suppurative destructive chronic cholangitis, extensive areas of confluent necrosis with hepatocytes regenerating into pseudorosettes, and numerous plasma cells. According to the Paris Criteria, the patient was then diagnosed with an autoimmune hepatitis-primary biliary cholangitis overlap syndrome (AIH-PBC-OS). After adding azathioprine and ursodeoxycholic acid to the treatment, there was a satisfactory response. This is the second worldwide report of an AIH-PBC-OS triggered by COVID-19, but the first case with a negative anti-mitochondrial antibody. In this setting, histologic evaluation of the liver by an experienced pathologist is a hallmark of achieving the diagnosis and correctly treat the patient.

Evaluation of the Hepatocellular Carcinoma Predictive Scores PAGE-B and mPAGE-B among Brazilian Patients with Chronic Hepatitis B Virus Infection.

Hepatitis B virus (HBV) is intrinsically oncogenic and related to hepatocellular carcinoma (HCC). Predictive scores of HCC have been developed but have been poorly studied in admixed populations. Therefore, we aimed to evaluate the performance of PAGE-B and mPAGE-B scores for HCC prediction in HBV Brazilian patients and factors related to HCC occurrence. This is a retrospective study that evaluated patients followed at a tertiary university center. A total of 224 patients were included, with a median follow-up period of 9 years. The mean age at HBV diagnosis was 38.71 ± 14.19 years, predominantly males (66.1%). The cumulative incidence of HCC at 3, 5, and 7 years was 0.993%, 2.70%, and 5.25%, respectively, being related in the univariate logistic regression analysis to male sex (p = 0.0461), older age (p = 0.0001), cirrhosis at HBV diagnosis (p < 0.0001), and higher values of PAGE-B and mPAGE-B scores (p = 0.0002 and p < 0.0001, respectively). Older age, male sex, and cirrhosis at HBV diagnosis were independently associated with HCC occurrence. The AUROCs of PAGE-B and mPAGE-B were 0.7906 and 0.7904, respectively, with no differences between them (p = 0.9767). In conclusion, both PAGE-B and mPAGE-B showed a correct prediction of HCC above 70% in this cohort.

Prevalence of Hepatocellular Carcinoma and Its Characteristics in 10 Years of Transplantation in a University Hospital in Brazil.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, accounting for up to 90% of all primary liver neoplasms. HCC treatment options depend on tumor burden, the degree of liver dysfunction, and performance status. Orthotopic liver transplant offers the best chance for cure. The selection criteria adopted for transplant are based on the Milan Criteria (MC), which depend on tumor size and number (1 lesion ≤5 cm or up to 3 lesions of ≤3 cm, without vascular invasion or extrahepatic spread). In Brazil, an expanded version of the original MC, named the Brazilian Criteria (BC), takes into consideration only tumors larger or equal to 2 cm. This retrospective cohort aims to describe the prevalence of primary liver tumors and analyze the macro and microscopic characteristics of HCC on explant pathology in a university hospital over 10 years. Of 485 transplants, 243 (50.1%) had HCC. Most patients were men (77.4%) with a mean age of 58.4 years, and the most common primary etiology of liver disease was hepatitis C infection (64.2%). The total number of tumors was 628, generally multicentric (55.6%); segment VIII was the most affected, and alpha-fetoprotein was altered in 70.7% of the cases. Most patients had tumors meeting MC at pretransplant and on explant evaluation, along with higher overall survival when compared to those exceeding MC and BC, and especially with those outside both criteria. In addition, tumors outside MC represent an independent risk factor associated with death.

Direct-acting antivirals for chronic hepatitis C treatment: The experience of two tertiary university centers in Brazil.

BACKGROUND: Hepatitis C virus (HCV) treatment has undergone major changes in recent years. Previous interferon-based therapies have been replaced by oral direct-acting antivirals (DAA) regimens, with high sustained virologic response (SVR) rates, and a lower incidence of adverse events (AEs). AIM: To evaluate the efficacy and safety of DAAs for HCV treatment in subjects from two tertiary university centers in Brazil. METHODS: This is a multicenter retrospective cohort study of 532 patients with chronic hepatitis C (CHC), undergoing treatment with interferon-free regimens from November 2015 to November 2019. The therapeutic regimen was defined by the current Brazilian guidelines for HCV management at the time of treatment. Demographic, anthropometric, clinical, and laboratory variables were evaluated. SVRs were assessed at 12 to 24 wk after therapy by intention-to-treat (ITT), and modified ITT (m-ITT) analysis. AEs and serious adverse events (SAEs) were registered. In the statistical analysis, a P value of < 0.05 was considered significant. RESULTS: The mean age was 56.88 years, with 415 (78.5%) being HCV genotype 1, followed by genotype 3 (20.1%). Moreover, 306 (57.5%) subjects had cirrhosis, and a third of them had decompensated cirrhosis. Sofosbuvir (SOF) plus daclatasvir ± ribavirin was the most frequently used treatment (66.9%), followed by SOF plus simeprevir (21.2%). The overall ITT SVR was 92.6% (493/532), while the m-ITT SVR was 96.8% (493/509). Variables associated with treatment failure via ITT evaluation were hepatic encephalopathy (OR: 4.320; 95%CI: 1.920-9.721, P = 0.0004), presence of esophageal varices (OR: 2.381; 95%CI: 1.137-4.988, P = 0.0215), previous portal hypertensive bleeding (OR: 2.756; 95%CI: 1.173-6.471, P = 0.02), higher model for end-stage liver disease scores (OR: 1.143, 95%CI: 1.060-1.233, P = 0.0005), lower serum albumin levels (OR: 0.528, 95%CI: 0.322-0.867, P = 0.0115), higher serum creatinine (OR: 1.117, 95%CI: 1.056-1.312, P = 0.0033), and international normalized ratio (INR) levels (OR: 5.542, 95%CI: 2.023-15.182, P = 0.0009). AEs were reported in 41.1% (211/514) of patients, and SAEs in 3.7%. The female gender, higher body mass index, esophageal varices, higher INR values, and longer treatment duration were independently associated with AE occurrence. CONCLUSION: Treatment with oral DAAs attains a high SVR rate, with fewer SAEs in a real-life cohort of subjects with CHC, from two tertiary university centers in Brazil.