Ezequiel Ridruejo

Central hypothyroidism and hypophysitis during treatment of chronic hepatitis C with pegylated interferon alpha and ribavirin.

Thyroid dysfunction is a known complication of interferon treatment in patients with hepatitis C virus (HCV) infection. Other uncommon endocrine complications have been reported during the treatment of viral hepatitis with IFN-alpha, such as hypopituitarism. A 54-year-old female patient with chronic hepatitis C began treatment with pegylated (PEG)-IFN-alpha 2a 180 mug/week plus ribavirin 1,000 mg/day. At week 20 of treatment, her routine laboratory control showed low levels of thyroid-stimulating hormone (TSH) and free serum thyroxine. This was confirmed at week 24, and other laboratory values showed low levels of adrenocorticotrophic hormone (ACTH). A T1-weighted magnetic resonance imaging scan demonstrated high intensity of the anterior pituitary gland and enhancement after intravenous administration of gadolinium. Hypophysitis with hypothalamic-pituitary dysfunction and secondary or central hypothyroidism was diagnosed on the basis of the clinical features, endocrinological assessment, immunological markers and imaging studies. Twenty-four weeks after stopping treatment, HCV RNA was negative by polymerase chain reaction and alanine aminotransferase values were below the upper limits of normal, and ACTH and thyroid values remained within the reference values. This is the first report of central hypothyroidism and hypophysitis during treatment with PEG-IFN-alpha plus ribavirin, and may be included in the potential list of side effects of the combination treatment.

Severe cholestatic hepatitis as the first symptom of secondary syphilis.

A 57-year-old homosexual patient with controlled hypertension and hyperlipidaemia was referred to us for assessment of a 3-week history of generalized fatigue, anorexia, low-grade fever, and abnormal liver function tests. At physical examination the liver spam was 5 cm at the midclavicular line, he had no skin lesions or peripheral adenopathy. Laboratory evaluation showed the following: alkaline phosphatase (ALP), 1568 IU/L; AST, 139 IU/L; ALT, 315 IU/L; total bilirubin, 0.8 mg/dL; γ -globulins, 2.15 g/L (normal: <1.6 g/L); hematocrit, 35.9% (normal, 45–50%); hemoglobin, 12.4 g/dL (normal, 14–17 g/dL); and sedimentation rate, 93 mm/hr. The patient was on atorvastatin, 40 mg qd; atenolol, 50 mg qd; and aspirin, 325 mg qd. A complete laboratory workup done 2 months before the consultation was normal (Table 1). The patient had no history of recent exposure to hepatitis, drugs, tattoos, body piercing, or transfusions and denied alcohol consumption. Further laboratory tests showed the following: HAV IgG+ IgM−; EBV VCA IgG+ IgM−; CMV IgG+ IgM−; ANA−; ASMA 1/10; AMA 1/50, types 2 and 5; HIV−; anti-HCV; anti-

Safety of long-term nucleos(t)ide treatment in chronic hepatitis B.

Currently, five nucleos(t)ide analogs (NAs) are approved for the treatment of chronic hepatitis B (CHB) infection. They are lamivudine, adefovir dipivoxil, telbivudine, entecavir (ETV) and tenofovir disoproxil fumarate (TDF). Two of them, ETV and TDF, are recommended as first-line treatment options. Their main advantages include excellent tolerability, antiviral potency and a high genetic barrier to resistance within medium duration treatment periods (2 – 6 years). In most patients, NAs need to be administered on a long-term basis. Several studies suggest that NAs long-term administration have been associated with low rates of serious adverse events (AEs), including lactic acidosis, renal function impairment, osteopenia and osteoporosis. Discontinuations due to AEs tended to be low in published randomized clinical trial and in the experience in clinical practice. NAs long-term use appears to be safe and effective; and in patients with advanced liver disease, despite preliminary concerning reports, their short-term use also appears to be safe and effective. Although major AEs are infrequent, they can be initially clinically silent yet lead to serious medical problems, therefore, a proactive surveillance and their prompt management is recommended.

Safety of direct-acting antivirals in the treatment of chronic hepatitis C

Introduction: Combination therapy with pegylated interferon, ribavirin and the two first-generation NS3/4A protease inhibitors (PIs), telaprevir (TVR) and boceprevir (BOC), is the new standard-of-care therapy for patients who are chronically infected with genotype 1 hepatitis C virus. These combinations significantly increase sustained virological response (SVR) rates, but they also increase the rates of adverse events (AEs). Appearance of significant AEs may necessitate dose reduction or discontinuation of treatment, and may impact on virological response. Areas covered: In registration trials, IFN-related AEs were a dominant feature in both types of therapy. Some events were more frequent with PI-containing regimens, like anemia and dysgeusia with BOC and anemia, pruritus, rash and anorectal symptoms with TVR. This review addresses the early identification and management of AEs to improve tolerance, and to avoid reduction in SVR rates. Expert opinion: Every patient will experience adverse effects to differing degrees; a systematic approach to their management can be very helpful. Early recognition and intervention can help clinicians ensure that patients are able to complete therapy where possible and achieve the goal of viral eradication. Treatment with the next generation of antivirals will improve safety and efficacy.

Chylous ascites as the main manifestation of left ventricular dysfunction: a case report

BackgroundAscites is one of the most common complications of liver diseases, even though in 15% of the cases it is related to extrahepatic diseases; 3% are of cardiac nature and they appear associated with signs and symptoms of heart failure.Case presentationA 70 year old man was admitted with more than one year history of abdominal distension and a weight gain of 10 kilograms. He is asymptomatic and walks 2000–3000 meters a day without angor or dyspnea. The physical examination shows moderate abdominal distension, with no hepatosplenomegaly or edema, and there is mild jugular vein distension. The studies performed (complete laboratory work up, paracentesis, liver biopsy, echocardiogram, intrahepatic pressure measurements, etc.) showed a chylous ascites related to portal hypertension, and left ventricular dysfunction was the only probable cause found.ConclusionAsymptomatic heart dysfunction can mimic liver disease and should be kept in mind as a cause of chylous ascites.

Antiviral treatment for chronic hepatitis B in renal transplant patients

Chronic hepatitis B infection is frequent in renal transplant patients. It negatively impacts long term outcomes reducing graft and patient survival. Current guidelines clearly define who needs treatment, when to start, what is the first line therapy, how to monitor treatment response, when to stop, and how patients must be controlled for its safety. There is some data showing a favorable safety and efficacy profile of nucleos(t)ide analogue (NUC) treatment in the renal transplant setting. Entecavir, a drug without major signs of nephrotoxicity, appears to be the first option for NUC naïve patients and tenofovir remains the preferred choice for patients with previous resistance to lamivudine or any other NUC. Renal transplant recipients under antiHBV therapy should be monitored for its efficacy against HBV but also for its safety with a close renal monitoring. Studies including a large number of patients with long term treatment and follow up are still needed to better demonstrate the safety and efficacy of newer NUCs in this population.

Hepatotoxicity induced by coxibs: how concerned should we be?

ABSTRACT Introduction: The selective inhibitors of COX-2, coxibs, are nonsteroidal anti-inflammatory drugs (NSAIDs) that have much better gastrointestinal safety profile as compared with non-selective NSAIDs. In this review, we analyze both the epidemiological features of coxib-induced hepatotoxicity and the clinical impact of coxib-associated liver damage, based on literature data. Areas covered: We carried out a search of the databases MEDLINE (PubMed), LILACS and SCIELO, from December 1999 to January 2016, to retrieve studies exploring the real impact of coxibs in liver toxicity as compared to non-selective COX-2 inhibitor NSAIDs. Expert opinion: Although reliable data on the incidence of celecoxib- and etoricoxib-induced hepatotoxicity are lacking, because of cohort studies have been generally underpowered to detect hepatic events, coxibs have been scarcely related to hepatotoxicity. Hence, coxib-induced liver injury seems to be an uncommon event, yet exhibits a wide spectrum of damage. Increasing COX-2 drug selectivity, as for rofecoxib, valdecoxib, parecoxib, and lumiracoxib, has been associated with higher cardiovascular risk, as well as dermatological and serious hepatic reactions. The actual risk of liver toxicity from the currently approved coxibs compared with non-selective NSAIDs will be discussed. Finally, classical and novel molecular mechanisms of coxib-induced hepatotoxicity are also described.

Role of HLA-DP and HLA-DQ on the clearance of hepatitis B virus and the risk of chronic infection in a multiethnic population

HBV infection exhibits geographical variation in its distribution in South America. While HBV rates are low in central Argentina, the north‐western region exhibits intermediate HBV rates. Unfortunately, the reasons that could explain this difference are still unknown.

Ombitasvir/paritaprevir/ritonavir/dasabuvir ± ribavirin is safe and effective in HCV-infected patients in a real-life cohort from Latin America

Information about the use of ombitasvir/paritaprevir/ritonavir/dasabuvir ± ribavirin (OBV/PTV/r/DSV ± RBV) in real‐clinical practice in Latin America is scarce. We aimed to confirm safety and effectiveness of OBV/PTV/r/DSV ± RBV therapy in real‐world setting. We analyzed a cohort of patients with genotype 1 infection treated with OBV/PTV/r/DSV ± RBV. Data on demographics, clinical features, safety, and virological response were retrospectively collected from 21 centers in Latin America. A total of 96 patients received OBV/PTV/r/DSV, associated with RBV in 68% of the cases. Most were genotype 1b (80%), 56 (58%) had cirrhosis, and 45 (47%) failed prior HCV treatment. Adverse events occurred in 62% of patients. The most common adverse events were pruritus (21%), hyperbilirubinemia (17%), and asthenia (17%). Five patients discontinued therapy prematurely due to hepatic decompensation, three of them were Child‐Pugh B at baseline and one patient died due to multi‐organ failure. Follow up HCV‐RNA 12 weeks after completion of therapy was evaluated in all the patients and sustained virologic response rate was 97%. No virologic breakthrough was detected. Our study confirms that OBV/PTV/r/DSV treatment is highly effective in patients with chronic HCV without cirrhosis or with Child‐Pugh A cirrhosis in non‐European populations. Adverse events were often mild and rarely led to treatment discontinuation except for patients with Child‐Pugh B cirrhosis or with previous history of hepatic decompensation. These results can support the development of public strategies to expand the access of OBV/PTV/r + DSV and other DAAs combinations in order to reduce the burden of HCV infection in our region.

Pre-treatment prediction of response to peginterferon plus ribavirin in chronic hepatitis C genotype 3

AIM To evaluate pre-treatment factors associated with sustained virological response (SVR) in patients with hepatitis C virus (HCV) genotype 3 treated with peginterferon and ribavirin (RBV). METHODS We retrospectively analyzed treatment naive, mono-infected HCV genotype 3 patients treated with peginterferon and RBV. Exclusion criteria included presence of other liver disease, alcohol consumption and African American or Asian ethnicity. The variables collected and compared between patients who achieved an SVR and patients who did not were as follows: gender, age, fibrosis stage, diabetes, body mass index, steatosis, INFL3 polymorphism, pre-treatment HCV-RNA, type of peginterferon, RBV dose and adherence. RESULTS A total of 107 patients treated between June, 2004 and March, 2013 were included. Mean treatment duration was 25.1 (± 1.8) wk. Overall, 58% (62/107) of the patients achieved an SVR and 42% (45/107) did not. In the multivariate logistic regression analysis, pre-treatment HCV-RNA ≥ 600000 UI/mL (OR = 0.375, 95%CI: 0.153-0.919, P = 0.032) and advanced fibrosis (OR = 0.278, 95%CI: 0.113-0.684, P = 0.005) were significantly associated with low SVR rates. In patients with pre-treatment HCV-RNA ≥ 600000 UI/mL and advanced fibrosis, the probability of achieving an SVR was 29% (95%CI: 13.1-45.2). In patients with pre-treatment HCV-RNA < 600000 UI/mL and mild to moderate fibrosis, the probability of achieving an SVR was 81% (95%CI: 68.8-93.4). CONCLUSION In patients with HCV genotype 3 infections the presence of advance fibrosis and high pre-treatment viral load might be associated with poor response to peginterferon plus RBV. These patients could benefit the most from new direct antiviral agents-based regimes.