Primary biliary cholangitis: a rare diagnosis during pregnancy.

Primary biliary cholangitis is an autoimmune disease that mostly affects women. It is uncommon in women of childbearing age and the diagnosis during pregnancy is rare and can be challenging. Described here is a case of primary biliary cholangitis first manifesting during pregnancy, with the onset of pruritus, jaundice, biochemical liver abnormalities and positive antimitochondrial antibodies. Although treatment with ursodeoxycholic acid was started at the time of diagnosis, there was a progressive worsening of cholestatic biochemical markers throughout pregnancy. In addition, fasting hyperglycemia with polyhydramnios was diagnosed, consistent with gestational diabetes. She had a spontaneous preterm delivery at 31 weeks of gestation, of a newborn who was admitted to the neonatal intensive care unit but who subsequently had no long-term sequelae of preterm delivery. A maternal postpartum flare occurred. Treatment with ursodeoxycholic acid was well tolerated during pregnancy and lactation.

Gynecological history to diagnosis and pregnancy outcomes in diagnosed Wilson's disease patients under therapy - A bicentric matched-control cohort study.

INTRODUCTION: most studies narrowly focus on pregnancy outcome comparisons between Wilson's disease (WD) patients on and off treatment. We aimed to identify menses irregularities in untreated WD, and to evaluate pregnancy outcomes in treated WD patients as compared to matched controls (with and without liver disease). METHODS: females with WD, hepatitis C (liver disease controls), and other gastrointestinal conditions (controls without liver disease) were identified at two tertiary hospital gastroenterology departments. Gynecological and obstetric data were retrospectively collected. A comparison of gynecological and obstetric outcomes was performed between the groups, and regression models were used to further assess obstetric outcomes. RESULTS: a total of 18 females with WD were identified, comprising 19 pregnancies under treatment in 11 patients, and 20 females were included in each control group. Age and liver disease stage were adjusted between groups. The incidence of menses irregularities was higher for WD (late menarche, 83 % vs. 10 % vs. 10 %, p < 0.01; irregular cycles, 100 % vs. 20 % vs. 20 %, p < 0.01; amenorrhea, 67 % vs. 10 % vs. 5 %, p < 0.01). Logistic regression models identified WD as a predictor of miscarriage and low birth weight (OR: 6.0; CI: 1.1-33.3; p < 0.05) but not of birth defects. Neither therapies (D-penicillamine 300 mg or zinc acetate 150 mg) nor disease presentation (hepatic and/or neurological) were associated with obstetric complications in WD subjects. CONCLUSION: there was a higher incidence of menses irregularities in untreated females with WD. In addition, our data suggest that treated WD still carries a higher risk of spontaneous abortion and low birth weight when compared to matched control groups with and without liver disease.

Predictors for incomplete response to ursodeoxycholic acid in primary biliary cholangitis. Data from a national registry of liver disease.

BACKGROUND: The current standard of treatment in primary biliary cholangitis (PBC) is ursodeoxycholic acid (UDCA), although a considerable proportion of patients show incomplete response resulting in disease progression. OBJECTIVE: This study aimed to assess the prevalence of incomplete response to UDCA and determine associated patients' characteristics. METHODS: Patients with PBC as main diagnosis were included from a national multicentric patient registry-Liver.pt. Main endpoints included incomplete response to UDCA treatment according to Barcelona, Paris I and Paris II criteria, Globe and UK PBC scores and the association between baseline characteristics and incomplete response according to Paris II criteria. RESULTS: A total of 434 PBC patients were identified, with a mean age of 55 years and 89.2% females. Nearly half of patients were asymptomatic at diagnosis and 93.2% had positive anti-mitochondrial antibodies. Almost all patients (95.6%) had been prescribed at least one drug for PBC treatment. At the last follow-up visit, 93.3% were under treatment of which 99.8% received UDCA. Incomplete response to UDCA was observed in 30.7%, 35.3%, 53.7% and 36.4% of patients according to Barcelona, Paris I, Paris II criteria and Globe score, respectively. After adjusting for age and sex, and accordingly to Paris II criteria, the risk for incomplete biochemical response was 25% higher for patients with cirrhosis at diagnosis (odds ratio [OR] = 1.25; 95% confidence interval [95%CI]: 1.02-1.54; p = 0.033) and 35% (95%CI:1.06-1.72; p = 0.016) and 5% (OR = 1.05; 95%CI:1.01-1.10; p = 0.013) for those with elevated gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP). CONCLUSION: A considerable proportion of patients showed incomplete biochemical response to UDCA treatment according to Paris II criteria. Cirrhosis, elevated GGT and ALP at diagnosis were identified as associated risk factors for incomplete response. Early identification of patients at risk of incomplete response could improve treatment care and guide clinical decision to a more careful patient monitorization.

Burden of Liver Cirrhosis in Portugal between 2010 and 2017.

INTRODUCTION: Liver cirrhosis is a prevalent disease in Portugal. Recent changes in alcohol consumption, as well as the wide use of direct-acting antivirals for hepatitis C since 2015, may be contributing to changes in the national burden of liver cirrhosis in the last few years. OBJECTIVES: We aim to characterize the burden of cirrhosis in Portugal between 2010 and 2017. PATIENTS AND METHODS: We analyzed all hospital admission episodes due to cirrhosis in Portugal Mainland between 2010 and 2017, registered in the national Diagnosis-Related Group database, according to etiology of cirrhosis. We also analyzed data on mortality and potential years of life lost from liver cirrhosis and chronic liver disease, retrieved from Statistics Portugal (National Institute for Statistics). RESULTS: Between 2010 and 2017, a total of 51,438 admissions for liver cirrhosis occurred in Portugal. The annual number of admissions decreased (p = 0.044) during the analyzed period. The most frequent cause of cirrhosis was alcoholic liver disease, present in 78.9% of all admissions (n = 40,595), followed by chronic hepatitis C virus infection, present in 11.3% (n = 5,823). A male predominance was identified in the admissions for every analyzed cause of cirrhosis. Annual admissions for alcoholic cirrhosis remained stable (p = 0.075) during the 8-year period. The same stable tendency was observed in the number of admissions for cirrhosis caused by hepatitis C virus (p = 0.861) and alcohol plus hepatitis C virus infection (p = 0.082), although these admissions for hepatitis C-related cirrhosis increased until 2014-2015 and steadily decreased thereafter. Annual deaths due to liver cirrhosis and chronic liver disease decreased from 1,357 in 2010 to 1,038 in 2017 (p = 0.002). The number of potential years of life lost decreased as well in the period (p = 0.001). CONCLUSION: The burden of cirrhosis, evaluated by hospital admissions, mortality, and potential years of life lost, decreased in Portugal between 2010 and 2017.

INTRODUÇÃO: A cirrose hepática é uma patologia prevalente em Portugal. Alterações recentes no consumo de álcool, assim como o uso generalizado de antivíricos de ação direta para a hepatite C desde 2015, podem estar a contribuir para alterações no peso nacional da cirrose hepática nos últimos anos. OBJETIVOS: Pretendemos caracterizar o impacto da cirrose em Portugal entre 2010 e 2017. DOENTES E MÉTODOS: Analisámos todos os episódios de internamento hospitalar por cirrose em Portugal Continental entre 2010 e 2017, registados na base de dados dos Grupo de Diagnósticos Homogéneos, de acordo com a etiologia da cirrose. Também analisámos dados de mortalidade e anos de vida potencialmente perdidos por cirrose e doença hepática crónica, disponibilizados pelo Instituto Nacional de Estatística. RESULTADOS: Entre 2010 e 2017 ocorreram 51 438 internamentos por cirrose hepática em Portugal. O número total de internamentos diminuiu (p = 0,044) durante o período analisado. A causa mais frequente de cirrose foi doença hepática alcoólica, presente em 78,9% de todos os internamentos (n = 40 595), seguido da infeção crónica pelo vírus da hepatite C, presente em 11,3% (n = 5 823). Verificou-se predominância de doentes do género masculino em todas as causas de cirrose analisadas. O número de internamentos anual por cirrose alcoólica manteve-se estável (p = 0,075) durante os 8 anos. A mesma tendência foi observada no número de internamentos por infeção por vírus de hepatite C (p = 0,861) e álcool mais infeção por vírus de hepatite C (p = 0,082) − embora estes internamentos por cirrose relacionada com hepatite C tenham aumentado até 2014­2015 e depois diminuído sustentadamente. O número anual de óbitos por cirrose e doença hepática crónica diminuiu de 1357 em 2010 para 1038 em 2017 (p = 0,002). O número de anos potenciais de vida perdidos diminuiu também (p = 0,001) nesse período. Conclusão: O impacto da cirrose, avaliado através dos internamentos hospitalares, mortalidade e anos potenciais de vida perdidos, diminuiu em Portugal entre 2010 e 2017.

Primary Liver Lymphoma Presenting as Liver Nodules.

The liver is usually affected in advanced stages of lympho-proliferative diseases, but primary liver lymphomas (PLLs) are rare. The diagnosis is usually late, especially in patients without identifiable risk factors, with consequent worse prognosis. We report the case of a 59-year-old female with progressive worsening pain in the right hypochondrium and weight loss. She was previously healthy and had a family history of gastrointestinal and gynecologic neoplasms. During the initial investigation, three liver nodules suggestive of liver metastases were found. Nevertheless, no primary neoplasm was identified in a subsequent evaluation with imaging and endoscopic exams. Laboratory exams excluded hepatic infections, metabolic diseases, and acquired immunosuppression. Biopsy of the lesions revealed diffuse large B-cell lymphoma. Lymph node and medullar involvement were excluded, and the diagnosis of PLL was assumed. The patient started chemotherapy with R-CHOP. With this case, we intend to alert for this differential diagnosis of liver nodules, even in the absence of predisposing conditions for lymphoma. We point out the need to define universal diagnosis criteria for this pathology.

O fígado é geralmente afetado em estádios avançados de doenças linfoproliferativas, mas os linfomas primários do fígado são raros. O diagnóstico é habitualmente tardio, principalmente em doente sem fatores de risco identificados, e consequentemente com pior prognóstico. Apresentamos o caso de uma doente de 59 anos, com quadro álgico de intensidade crescente no hipocôndrio direito e perda ponderal. A doente era previamente saudável e tinha história familiar de neoplasia gastrointestinal e ginecológica. No estudo inicial, foram identificadas três imagens nodulares hepáticas sugestivas de metástases. No entanto, não se identificou tumor primário em exames de imagem nem endoscópicos. Foram também excluidas infeções hepáticas, doença metabólica e imunossupressão adquirida. A biópsia das lesões hepáticas revelou tratar-se de linfoma B difuso de grandes células. Foi excluido envolvimento ganglionar e medular pelo que se assumiu o diagnóstico de Linfoma Primário do Fígado. A doente iniciou quimioterapia com R-CHOP. Com este caso pretendemos alertar para a necessidade de equacionar este diagnóstico diferencial de nodulos hepáticos, mesmo na ausência de fatores de risco para linfoma. Também alertamos para a necessidade de se definirem critérios diagnósticos universais para esta patologia.

Retrospective Study of Transjugular Intrahepatic Portosystemic Shunt Placement for Cirrhotic Portal Hypertension.

BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) is used for decompressing clinically significant portal hypertension. The aims of this study were to evaluate clinical outcomes and adverse events associated with this procedure. METHODS: Retrospective single-center study including 78 patients submitted to TIPS placement between January 2015 and November 2018. Follow-up data were missing in 27 patients, and finally 51 patients were included in the study sample. Data collected from individual registries included demographics, comorbidities, laboratory results, complications, and clinical results according to the indication. RESULTS: Average pre-TIPS portosystemic pressure gradient decreased from 18.1 ± 5 to 6 ± 3 mm Hg after TIPS placement. Indications for TIPS were refractory ascites (63%, n = 49), recurrent or uncontrolled variceal bleeding (36%, n = 28), and Budd-Chiari syndrome (1.3%, n = 1). TIPS-related adverse events occurred in 29/51 (56.8%) patients, with hepatic encephalopathy (HE) in 21 (41%) patients, sepsis in 3, liver failure in 2, hemolytic anemia in 1, acute pulmonary edema in 1, and capsular perforation in 1 patient. Mean follow-up was 15.7 ± 15 months. First-month mortality was 11.7% (n = 6) (sepsis, n = 3; acute liver failure, n = 2; and recurrence of variceal bleeding, n = 1) and was significantly higher for patients with Child-Pugh >9 points (p = 0.01), model of end-stage liver disease (MELD) scores >19 (p = 0.02), and for patients with a history of HE before the procedure (p = 0.001). Older age (p = 0.006) and higher levels of creatinine (p = 0.008) were significantly higher in patients developing HE after TIPS. Ascites persisted in 21.2% (7/33 patients) and was more frequent in patients with lower baseline albumin levels (p = 0.003). Recurrent variceal bleeding occurred in 22% (n = 4/18 patients) and was more frequent in patients with lower baseline hemoglobin levels (p = 0.03). CONCLUSION: TIPS is effective in up to 80% of patients presenting with variceal bleeding or refractory ascites. Careful patient selection based on age and HE history may reduce adverse events after TIPS.

INTRODUÇÃO E OBJECTIVOS: O shunt portossistémico transjugular intra-hepático (TIPS) é usado para descompressão de hipertensão portal hepática clinicamente significativa. Os objetivos deste estudo foram avaliar os resultados clínicos e efeitos adversos associados a este procedimento. MÉTODOS: Estudo retrospectivo de centro único, incluindo 78 pacientes submetidos ao procedimento entre Janeiro de 2015 e Novembro de 2018. Os dados de seguimento estavam ausentes em 27 doentes, tendo sido incluidos 51 doentes na análise. Os dados colhidos de registos individuais incluíram dados demográficos, comorbilidades, resultados laboratoriais, complicações e resultados clínicos, de acordo com a indicação. RESULTADOS: O gradiente médio de pressão portossistémica pré-TIPS foi de 18.1 ± 5 mm Hg, quediminuiu para 6 ± 3 mm Hg. Indicações para TIPS foram ascite refratária (65%, n = 33) e hemorragia varicosa recorrente/refratária (35%, n = 18). As complicações relacionadas ao TIPS ocorreram em 29 doentes (56.8%): encefalopatia hepática (EH) em 21 doentes, sépsis (n = 3), insuficiencia hepática (n = 2), anemia hemolítica (n = 1), edema pulmonar agudo (n = 1) e perfuração capsular (n = 1). O seguimento médio foi de 15.7 ± 15 meses. A mortalidade no primeiro mes foi de 11.7% (n = 6) (sépsis, n = 3; insuficiencia hepática aguda, n = 2; recorrência de hemorragia varicosa, n = 1), e foi significativamente mais frequente em doentes com Child-Pugh >9 pontos (p = 0.01), pontuação de MELD >19 pontos (p = 0.02) e história de EH prévia ao procedimento (p = 0.001). Doentes que desenvolveram EH tinha mais frequentemente idade avançada (p = 0.006) e níveis mais elevados de creatinina (p = 0.008). A ascite persistiu em 21.2% (7/33 doentes), mais habitualmente em doentes com níveis mais baixos de albumina basai (p = 0.003). Hemorragia varicosa recorrente ocorreu em 22% (n = 4/18 doentes), em associação com níveis mais baixos de hemoglobina (p = 0.03). CONCLUSÃO: O TIPS é eficaz em 80% dos doentes que apresentam hemorragia varicosa ou ascite refratária. Eventos adversos podem ser reduzidos através da seleção de doentes, com base na idade e história de EH.

Efficacy of Glecaprevir/Pibrentasvir for 8 or 12 Weeks in Patients With Hepatitis C Virus Genotype 2, 4, 5, or 6 Infection Without Cirrhosis.

BACKGROUND & AIMS: Hepatitis C virus (HCV) has high genotypic diversity and global distribution. Agents that are effective against all major HCV genotypes, with shorter treatment duration, are needed to reduce disease burden. Glecaprevir (an NS3/4A protease inhibitor) and pibrentasvir (an NS5A inhibitor) have a high barrier to resistance and synergistic antiviral activity. We evaluated the safety and efficacy of 8 and 12 weeks' treatment with glecaprevir/pibrentasvir in patients with HCV genotype 2, 4, 5, or 6 infection without cirrhosis in 3 separate phase 3 trials. METHODS: We performed 2 open label, single-arm studies (SURVEYOR-II, Part 4 and ENDURANCE-4) and a randomized, double-blind, placebo-controlled study (ENDURANCE-2). In the ENDURANCE-2 study, adult patients with untreated or previously treated HCV genotype 2 infection without cirrhosis were randomly assigned (2:1) to groups given once-daily oral glecaprevir/pibrentasvir (n = 202; 300 mg/120 mg) or placebo (n = 100) for 12 weeks. In the SURVEYOR-II, Part 4 and ENDURANCE-4 studies, adult patients with untreated or previously treated patients with HCV genotype 2, genotype 4, genotype 5, or genotype 6 infection, without cirrhosis, were given once-daily oral glecaprevir/pibrentasvir (n = 121 in ENDURANCE-4 and n = 145 in SURVEYOR-II) for 12 or 8 weeks, respectively. In all studies the primary endpoint was sustained virologic response at 12 weeks after treatment (SVR12) in the intention-to-treat population. RESULTS: Among patients receiving glecaprevir/pibrentasvir for 8 weeks, rates of SVR12 were 98% (95% CI, 94.1-99.3) in those infected with HCV genotype 2 and 93% (95% CI, 83.6-97.3) in those infected with HCV genotypes 4, 5, or 6. Among patients receiving glecaprevir/pibrentasvir for 12 weeks, rates of SVR12 were 99.5% (95% CI, 98.5-100) in those infected with HCV genotype 2 and 99% (95% CI, 97.6-100) in those infected with HCV genotype 4, 5, or 6. No virologic failures occurred in patients with HCV genotype 4, 5, or 6 infections. The frequency and severity of adverse events in patients receiving glecaprevir/pibrentasvir were similar to those of patients who received placebo. CONCLUSION: In 3 Phase 3 studies, 8 weeks' treatment with glecaprevir/pibrentasivr produced an SVR12 in at least 93% of patients with chronic HCV genotype 2, 4, 5, or 6 infection without cirrhosis, with virologic failure in less than 1%. The drug combination had a safety profile comparable to 12 week's treatment with glecaprevir/pibrentasvir. ClinicalTrials.gov numbers: NCT02640482 (ENDURANCE-2), NCT02636595 (ENDURANCE-4), and NCT02243293 (SURVEYOR-II).

Baveno VI Recommendation on Avoidance of Screening Endoscopy in Cirrhotic Patients: Are We There Yet?

INTRODUCTION: Recent studies assessed the predictive value of liver transient elastography, combined or not with platelet count, for the presence of esophageal varices in patients with liver cirrhosis, and multiple cutoffs have been proposed. The Baveno VI consensus states that patients with compensated advanced chronic liver disease, liver stiffness <20 kPa, and a platelet count >150,000 have a very low risk of having varices requiring treatment and can avoid screening endoscopy. We aimed to validate this recommendation in a cohort of cirrhotic patients. METHODS: Retrospective analysis of all patients evaluated at the Gastroenterology Department (Centro Hospitalar de Lisboa Central) between September 2009 and October 2015 with a liver stiffness (FibroScan®) compatible with liver cirrhosis as well as upper endoscopy and blood tests within 12 months from elastography. Patients on propranolol ≥80 mg/day or carvedilol ≥12.5 mg/day, as well as those with previous variceal bleeding, variceal endoscopic treatments, or cirrhosis decompensations were excluded. We validated the new Baveno VI recommendation and explored alternative cutoffs. RESULTS: Ninety-seven patients were analyzed, 76.3% (74/97) male, mean age 54.3 ± 11.2 years. Most patients (55.7%) had no varices and 14.4% had varices requiring treatment. Most patients (78.4%) had cirrhosis related to chronic hepatitis C. If the new Baveno VI recommendation had been applied to this cohort, upper endoscopy would have been avoided in 11.3% (11/97) of patients, none of them with esophageal varices requiring treatment: specificity 100%, sensitivity 13.3%, positive predictive value 100%, and negative predictive value 16.3% for absence of varices requiring treatment. If screening endoscopy had been avoided in those patients with liver stiffness <30 kPa and platelet count ≥120,000, endoscopy would have been avoided in 27.8% (27/97) of patients, none of whom with esophageal varices requiring treatment: specificity 100%, sensitivity 32.5%, positive predictive value 100%, and negative predictive value 20% for absence of varices requiring treatment. CONCLUSIONS: The new Baveno VI criteria identified compensated cirrhotic patients without varices requiring treatment in whom screening endoscopy could have been avoided safely. Further studies are needed to confirm these findings and potentially explore more ambitious but still safe cutoffs for those criteria.

Epidemiology of hepatitis B in Portugal.

The epidemiology of hepatitis B in Portugal is insufficiently characterized. We aimed to review the epidemiology of hepatitis B in Portugal since 1980. A literature review was performed in MEDLINE, Scielo, Web of Science, and the Portuguese Scientific Repository for studies containing 'Hepatitis B' and 'Portugal' published from 1980 to June 2016. The initial search was complemented by abstract books from national gastroenterology and hepatology meetings and reports from the Service for Intervention on Addictive Behaviours and Dependences, the Portuguese Blood Institute, and Directorate-General of Health. Further studies were identified in references of retrieved papers and https://www.google.pt. Ninety references were included. Hepatitis B surface antigen (HBsAg) prevalence was up to 2% in the general population and decreased in the last decades: 1.13-2.0% in studies carried out in 1980-1989 and 0.02-1.45% in studies carried out in 1990-2014. Among pregnant women, HBsAg prevalence was 1.35% in those on primary care, but 6.2% among risk parturients. Among drug abusers, HBsAg prevalence decreased from 10-19.6% in the decades of 1980-1990 to 4.8% in 2014. Higher HBsAg prevalence rates were observed among populations of African or Asian origin. Individuals with hepatitis B were mostly men, mean age 36.9-49 years. The most frequent viral genotype was D. Genotype E is more prevalent in patient cohorts from Central-Southern Portugal (10-62%) than those from Northern Portugal (1-4.1%). The proportion of inactive carriers varied from 24.2 to 73%. The prevalence of cirrhosis varied from 5.8 to 23.7%. Portugal is a low-endemicity country for hepatitis B. Nevertheless, prevalence is high among specific subgroups that may benefit from specifically designed healthcare programs.

HCVerso1 and 2: faldaprevir with deleobuvir (BI 207127) and ribavirin for treatment-naïve patients with chronic hepatitis C virus genotype-1b infection.

The interferon-free combination of once-daily faldaprevir 120 mg, twice-daily deleobuvir 600 mg, and weight-based ribavirin was evaluated in two Phase III studies (HCVerso1, HCVerso2) in hepatitis C virus genotype-1b-infected, treatment-naïve patients, including those ineligible for peginterferon (HCVerso2). Patients without cirrhosis were randomized to 16 weeks (Arm 1; n=208 HCVerso1, n=213 HCVerso2) or 24 weeks (Arm 2; n=211 in both studies) of faldaprevir + deleobuvir + ribavirin. Patients with compensated cirrhosis received open-label faldaprevir + deleobuvir + ribavirin for 24 weeks (Arm 3; n=51, n=72). Primary endpoints were comparisons of adjusted sustained virologic response (SVR) rates with historical rates: 71% (HCVerso1) and 68% (HCVerso2). Adjusted SVR12 rates were significantly greater than historical controls for Arms 1 and 2 in HCVerso2 (76%, 95% confidence interval [CI] 71-81, P=0.002; 81%, 95% CI 76-86, P<0.0001) and Arm 2 in HCVerso1 (81%, 95% CI 77-86, P<0.0001), but not for Arm 1 of HCVerso1 (72%, 95% CI 66-77, P=0.3989). Unadjusted SVR12 rates in Arms 1, 2, and 3 were 71.6%, 82.5%, and 72.5%, respectively, in HCVerso1 and 75.6%, 82.0%, and 73.6%, respectively, in HCVerso2. Virologic breakthrough and relapse occurred in 24-week arms in 8%-9% and 1% of patients, respectively, and in 16-week arms in 7%-8% and 9%-11% of patients, respectively. The most common adverse events were nausea (46%-61%) and vomiting (29%-35%). Adverse events resulted in discontinuation of all medications in 6%-8% of patients. In treatment-naïve patients with hepatitis C virus genotype-1b infection, with or without cirrhosis, faldaprevir + deleobuvir + ribavirin treatment for 24 weeks resulted in adjusted SVR12 rates significantly higher than historical controls. Both studies were registered in ClinicalTrials.gov (NCT01732796, NCT01728324).

Spontaneous clearance of hepatitis C virus during alcoholic hepatitis: the alcohol killed the virus?

Spontaneous clearance of hepatitis C virus during chronic infection is uncommon. We report the case of a patient who cleared hepatitis C virus during an episode of presumed alcoholic hepatitis. A brief discussion on the immunological aspects of chronic hepatitis C and the impact of alcohol consumption on it is presented as well.

Ten years of hospital admissions for liver cirrhosis in Portugal.

BACKGROUND AND AIMS: More data on epidemiology of liver diseases in Europe are needed. We aimed to characterize hospital admissions for liver cirrhosis in Portugal during the past decade. PATIENTS AND METHODS: We analyzed all hospital admissions for cirrhosis in Portugal Mainland between 2003 and 2012 registered in the national Diagnosis-Related Group database. Cirrhosis was classified according to etiology considering alcohol, hepatitis B, and hepatitis C. RESULTS: Between 2003 and 2012, there were 63,910 admissions for cirrhosis in Portugal Mainland; 74.4% involved male patients. Etiologies of admitted cirrhosis were as follows: 76.0% alcoholic, 1.1% hepatitis B, 1.4% hepatitis B plus alcohol, 3.6% hepatitis C, and 4.0% hepatitis C plus alcohol. There was a significant decline (P<0.001) in admissions for alcoholic cirrhosis, whereas hospitalizations for cirrhosis caused by hepatitis C or hepatitis C plus alcohol increased by almost 50% (P<0.001). Patients admitted with alcoholic plus hepatitis B or C cirrhosis were significantly younger than those with either alcoholic or viral cirrhosis (53.1 vs. 59.4 years, respectively, P<0.001). Hospitalization rates for cirrhosis were 124.4/100,000 in men and 32.6/100,000 in women. Hepatocellular carcinoma and fluid retention were more common in viral cirrhosis, whereas encephalopathy and variceal bleeding were more frequent in alcoholic cirrhosis. Hepatorenal syndrome was the strongest predictor of mortality among cirrhosis complications (odds ratio 12.97; 95% confidence interval 11.95-14.09). In-hospital mortality was 15.2%. CONCLUSION: Despite the decline in admissions for alcoholic cirrhosis and the increase in those related to hepatitis C, the observed burden of hospitalized liver cirrhosis in Portugal was essentially attributable to alcoholic liver disease.

STARTVerso1: A randomized trial of faldaprevir plus pegylated interferon/ribavirin for chronic HCV genotype-1 infection.

BACKGROUND & AIMS: The efficacy and tolerability of faldaprevir, a potent hepatitis C virus (HCV) NS3/4A protease inhibitor, plus peginterferon (PegIFN) and ribavirin (RBV) was assessed in a double-blind, placebo-controlled phase 3 study of treatment-naïve patients with HCV genotype-1 infection. METHODS: Patients were randomly assigned (1:2:2) to PegIFN/RBV plus: placebo (arm 1, n = 132) for 24 weeks; faldaprevir (120 mg, once daily) for 12 or 24 weeks (arm 2, n = 259); or faldaprevir (240 mg, once daily) for 12 weeks (arm 3, n = 261). In arms 2 and 3, patients with early treatment success (HCV-RNA <25 IU/ml at week 4 and undetectable at week 8) stopped all treatment at week 24. Other patients received PegIFN/RBV until week 48 unless they met futility criteria. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). RESULTS: SVR12 was achieved by 52%, 79%, and 80% of patients in arms 1, 2, and 3, respectively (estimated difference for arms 2 and 3 vs. arm 1: 27%, 95% confidence interval 17%-36%; and 29%, 95% confidence interval, 19%-38%, respectively; p < 0.0001 for both). Early treatment success was achieved by 87% (arm 2) and 89% (arm 3) of patients, of whom 86% and 89% achieved SVR12. Adverse event rates were similar among groups; few adverse events led to discontinuation of all regimen components. CONCLUSIONS: Faldaprevir plus PegIFN/RBV significantly increased SVR12, compared with PegIFN/RBV, in treatment-naïve patients with HCV genotype-1 infection. No differences were seen in responses of patients given faldaprevir once daily at 120 or 240 mg.

Chronic hepatitis C treated with peginterferon alfa plus ribavirin in clinical practice.

BACKGROUND/AIMS: The role of genotype and viremia were retrospectively evaluated on sustained virological response (SVR) rates in routine clinical practice. METHODOLOGY: From 1907 patients with chronic hepatitis C proposed for treatment, we analysed 1380 (1124 naive and 256 treatment-experienced) with complete follow-up. Genotype and HCV RNA quantification were assayed by commercial tests. Viremia was considered high if >800,000IU/mL, and low if <400,000IU/mL. Liver fibrosis was staged in 614 patients. RESULTS: Genotype 1 was the most frequent (60%), followed by 3 (25%), 4 (9%) and 2 (2%); 3.2% had other or unclassified genotype. Genotype 1 was more prevalent in central Portugal and genotype 4 in the south. Viremia was =800,000IU/mL in 54.6% and <400,000IU/mL in 34.6% of the patients, particularly in genotype 2 (p<0.03) and 4 (p<0.001). Genotype non-1 had a significantly lower viral load (p=0.004). Mild or moderate fibrosis was present in 71.7% and bridging fibrosis or cirrhosis in 28.3%, with no differences among genotypes. Treatment was discontinued in 19.8%. SVR was achieved in 55.3% of naive and 36.3% of re-treated patients. CONCLUSIONS: Standard treatment of chronic hepatitis C in real-life achieves similar results obtained in clinical trials, despite differences of demographic and viral parameters.

[Treatment of HBV HCV co-infection: exceeded response]. / Tratamento da co-infecção do virus da hepatite B e C: resposta excedida.

Hepatitis B (HBV) and hepatitis C (HCV) are the most common causes of chronic liver disease. Due to shared routes of transmission, co-infection with HBV and HCV is not uncommon. Higher rates of cirrhosis and hepatocelular carcinoma have been demonstrated in HBV/HCV co-infected patients. No treatment standard has been established for HBV/HCV co-infected patients. Treatment decisions must be made based upon identification of the dominant virus, usually HCV, thus patients should receive pegylated interferon alpha with ribavirin as for HCV monoinfection. Sustained virological response rates for HCV are broadly comparable with HCV monoinfected patients. There is limited information regarding the benefit of combination with nucleos(t)ide analogues. Treatment decisions may modify the complex interaction between HBV and HCV, as flares of the untreated virus may occur, namely with reactivation of HBV. The authors report a case of HBV/HCV co-infection, without a dominant profile, in which the treatment response exceeded expectations regarding the available evidence.