Marco Olivera-Martinez

Health-related quality of life and depression in patients with chronic hepatitis C

BACKGROUND Hepatitis C is a major cause of liver disease worldwide. It has been associated with decreased health-related quality of life (HRQL) and psychiatric symptoms. Our aim was to assess HRQL, depression, and illness understanding in patients with chronic hepatitis C without previous interferon therapy. METHODS Consecutive patients attending a referral center were enrolled. HRQL was measured using SF-36 questionnaire, depression with Zung self-rating depression scale, and illness understanding with self-applied knowledge test. RESULTS Of 157 patients enrolled, 112 were female (71%) and 45 male (29%). Ninety-seven patients (61.8%) had cirrhosis. HRQL was significantly decreased in chronic hepatitis C patients compared to historical normal controls in all eight domains of the SF-36 (p < 0.001). In hepatitis C cirrhotic patients, HRQL was significantly lower among Child-Pugh class B and C subjects in domains reflecting physical health (p <0.05). Ninety-two patients (58.6%) had depression that resulted in lower HRQL when compared to nondepressed patients (p <0.05). One hundred fourteen patients (72.6%) had poor illness understanding of hepatitis C. These subjects had significantly lower HRQL scores in six of eight SF-36 domains when compared to patients with better understanding of the disease (p <0.05). CONCLUSIONS Chronic hepatitis C patients attending a tertiary-referral center had significant decrease in HRQL associated with depression (58.6%) and poor illness understanding (72.6%). Educational programs and their impact on HRQL need to be addressed in detail, particularly for the pre-treatment scenario.

Beyond the direct costs of hepatitis C treatment: the balance between costs and ethics.

Chronic HCV infection is a global health problem that can lead to cirrhosis and decompensated liver disease as well as hepatocellular carcinoma (HCC) in a substantial number of patients. It is the main indication for liver transplantation in the USA [1]. In resource-rich settings, the use of direct-acting antivirals (DAAs) has significantly improved the proportion of patients who achieve sustained virological response and tolerate therapy without drug toxicity otherwise associated with the use of pegylated interferon and ribavirin [2]. However, owing to the conflicting interests of pharmaceutical companies and insurance providers, many patients who would benefit from therapy are denied access to it. In this issue of Antiviral Therapy, Loy et al. published their study [3], which aimed to determine the amount of unbillable time and to estimate the financial burden of obtaining DAAs for HCV. The authors prospectively enrolled 52 patients who received sofosbuvir/ledipasvir or ombitasvir/paritaprevir/ritonavir/dasabuvir for genotype (GT) 1 and sofosbuvir/ribavirin for GT 2/3. The majority of these patients (56%) had private insurance and approximately 38% were denied prior authorization, necessitating an appeal. A total median time of 92.5 min of unbillable time per patient were imparted by non-physician providers (licensed nurses, registered nurses and advanced nurse practitioners) and were spent obtaining prior authorizations and appealing denials through the specialty pharmacy, reviewing medications and drug interactions, and educating patients. This time amounted to approximately

Re-treatment with Highly Purified nIFNα in Mexican Nonresponder Patients with Chronic Genotype 1 Hepatitis C

79 per patient. As expected, more time was spent on those patients requiring an appeal compared to those who did not. The study by Loy et al. [3] clearly demonstrates the presence of occult costs and barriers physicians and other health-care professionals encounter when embarking on HCV therapy with DAAs. The study also exposes a deeper problem: the conflicting interests of pharmaceutical companies and insurance providers. These two entities should ideally be aligned to the patient’s well-being and best interests. Instead, an ethical conundrum is exposed: equal access to health-care resources is not guaranteed for thousands of patients in need and this brings into question the principle of distributive justice. It is imperative that we remove insurance barriers to therapy, which would ultimately help reduce overall costs as shown in this study by unbillable time spent per patient. Beyond the minor occult cost of the 92 min spent per patient, it seems that insurance companies have been ignoring for quite some time the pharmacoeconomics of HCV treatment in the early stages of the disease. There are at least three well documented costeffectiveness studies from France, Ireland and Canada that demonstrate through Markov models, the advantages of treatment in patients with early stages of the disease as compared with the treatment of cirrhotic patients [4–6]. It is clear that some insurance companies delay or withhold these treatments in patients who are actively consuming alcohol. This is an archaic practice inherited from the time when pegylated interferon and ribavirin were the only available drugs for the treatment of the disease [7]. There is no evidence that this principle should be applied to DAAs and further studies are needed to support or reject this practice. Of note, in contrast to the Loy study, not all institutions have specialty pharmacies, and it may be plausible that those that do not, may have even higher amounts of unbillable time and other occult costs without a streamlined process in place to deal with obtaining prior authorizations and appealing denials. If we aim to treat more patients with HCV prior to progression to cirrhosis, HCC and even the need for liver transplantation, thereby avoiding the astronomical costs associated with these, we must have adequate resources in place, including the help of non-physician support staff. Moreover, this may facilitate the adoption of DAA therapy by non-gastroenterologists and Commentary

Hepatotoxicity Associated with Use of the Weight Loss Supplement Garcinia cambogia: A Case Report and Review of the Literature

BACKGROUND AND AIMS We undertook this study to evaluate the virological response to and presence of adverse events to natural interferon α (nIFNα; Multiferon®) treatment in previously nonresponsive Mexican patients chronically infected with genotype 1 hepatitis C. METHODS Thirty-nine patients received a 4-week induction of 5 days/week of 6 MU nIFNα plus weight-based ribavirin followed by 3 MU of nIFNα three times a week for 44 weeks. The relationship between viral response and incidence of adverse events was analyzed. RESULTS Early viral response (EVR) was age- and sex-dependent, with older male patients being less responsive. Sustained viral response (SVR) was evaluated according to: a) intention to treat analysis, b) 48-week treatment and 24-week follow-up (16 patients), and c) patients with EVR (11 patients). None of the factors was significantly different in groups a) and b); however, in group c) there was a better response with a marked viral load decline in younger patients and in patients aged 50 years and older. Five of 39 (13%) patients who completed treatment presented with an SVR. The most common adverse effect was asthenia in 27% of patients. CONCLUSIONS nIFNα could be a useful strategy for re-treatment in chronic hepatitis C, genotype 1, in previously nonresponsive patients. Confirmation of these data in a larger population is required.

Castleman’s Disease and Posttransplant Lymphoproliferative Disorder after Liver Transplant: 3-Year Follow-Up

The use of herbal and dietary supplements for weight loss is becoming increasingly common as obesity is becoming major health problem in the United States. Despite the popularity of these natural supplements, there are no guidelines for their therapeutic doses and their safety is always a concern. Garcinia cambogia extract with its active ingredient “hydroxycitric acid” is a component of many weight loss regimens. It suppresses fatty acid biosynthesis and decreases appetite. However, its prolonged use in weight maintenance is unknown. Here we describe a case of acute hepatitis after the use of Garcinia cambogia for weight loss.

Magnetic resonance elastography: Better, but still the same!

A 59-year-old male with a history of hepatitis C cirrhosis and history of hepatitis B exposure presented 8 months after orthotopic liver transplant (LT) with fever, fatigue, myalgia, night sweats, nonproductive cough, and shortness of breath. Bone marrow biopsy for pancytopenia was positive for Epstein-Barr virus (EBV) DNA. Lymph node biopsy for lymphadenopathy on imaging showed human herpes virus 8 (HHV8) associated Castlemans disease. Treatment included valganciclovir, rituximab, and prednisone taper with eventual discontinuation. Quantitative HHV8 DNA was initially 611,000 DNA copies/mL and was later undetectable at 6 months following treatment and remained undetectable at 3-year follow-up.

Hepatorenal Syndrome: Is It the Magnitude of the Renal Failure that Matters?

983-992. 2) Cavallin M, Kamath PS, Merli M, Fasolato S, Toniutto P, Salerno F, et al. Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: a randomized trial. HEPATOLOGY 2015;62:567-574. 3) Angeli P, Guarda S, Fasolato S, Miola E, Craighero R, Piccolo F, et al. Switch therapy with ciprofloxacin vs. intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in patients with cirrhosis: similar efficacy at lower cost. Aliment Pharmacol Ther 2006;23:75-84.

Erratum to: Hepatorenal Syndrome: Are We Missing Some Prognostic Factors?

To the Editor: Hepatorenal syndrome (HRS) is a serious and life threatening complication of end stage liver disease and the criteria for its diagnosis were defined in 1996 [1] and revisited in 2007 [2]. The first definition was a set of major and minor criteria where the renal function was considered abnormal if the creatinine was[1.5 mg/dL or the creatinine clearance was\40 mL/min. The new consensus considered impaired renal function as having a creatinine value [1.5 mg/dL without improvement after 48 h of diuretic withdrawal and volume expansion with intravenous albumin [1, 2]. Neither of these definitions takes into account the magnitude of the rise in creatinine and its association with the reversibility or prognosis of hepatorenal syndrome. In January 2012, our group published in this journal [3] the largest series of patients with HRS type 1 in the last 5 years according to the new Ascites Club definition of this disease. We described the etiology of the end stage liver disease (ESLD) and the serum creatinine as independent predictive factors for survival in HRS. In 2011, Boyer et al. [4] also published their work regarding response of HRS to treatment with terlipressin versus placebo, finding that serum creatinine is a prognostic factor for survival and HRS reversal, while MELD score and bilirubin did not have an independent prognostic value, confirming our results and even considering that serum creatinine might be the best predictor of HRS reversal. The same finding has been documented by Martin-Llahi et al. [5] in a study comparing terlipressin plus albumin with albumin alone in the reversal of HRS. What makes our results even more interesting, is the fact that terlipressin, considered in Europe and Latin America the standard of care for HRS, was not used in our population (we used midodrine and octreotide) and creatinine continues to be an independent strong prognostic factor for patient survival and HRS reversal. In the paper of Boyer et al. [4] it is emphasized that neither MELD score nor bilirubin are independent predictors of survival. This leaves again the creatinine level as the sole predictor of reversibility and survival. There are several questions to be answered regarding HRS and its prognosis: should we consider the creatinine level as the only variable prognosticating outcome? Is there a creatinine level at which treatment is futile? Is early treatment during HRS justified? Should we adopt terlipressin as our standard of treatment? Is terlipressin better than midodrine and octreotide? What is obvious is that HRS is a multisystem disease, recently re-defined, which might require further panel discussion, and probably the Ascites Club should have meetings during national and international conferences at regular intervals.

School-based hepatitis B immunization program in adolescents

The online version of the original article can be found underdoi:10.1007/s10620-011-1861-1.M. Olivera-Martinez S. D’ SouzaSection of Gastroenterology and Hepatology,University of Nebraska Medical Center,983040 Nebraska Medical Center,Omaha, NE 69198-3040, USAe-mail: molivera@unmc.eduS. D’ Souzae-mail: sdsouza@unmc.eduH. SaylesDepartment of Biostatistics, University of Nebraska MedicalCenter, 983040 Nebraska Medical Center,Omaha, NE 69198-3040, USAe-mail: hsayles@unmc.eduR. VivekanandanSection of Internal Medicine, University of Nebraska MedicalCenter, 983040 Nebraska Medical Center,Omaha, NE 69198-3040, USAe-mail: rvivekanandan@unmc.eduM. C. Florescu (&)Section of Nephrology, University of Nebraska Medical Center,983040 Nebraska Medical Center,Omaha, NE 69198-3040, USAe-mail: mflorescu@unmc.edu

Recurrent Viral Liver Disease (Hepatitis B and C) after Liver Transplantation

In Mexico a vaccine against hepatitis B virus (HBV) has been included in the national scheme of infant vaccination since 1999. However young adolescents and adults remain at risk of acquiring the virus. This letter to the editor presents a study on the compliance of an adolescent school-based vaccination program with a two-dose schedule against HBV. Hepatitis B recombinant vaccine 20 mcg was administered intramuscularly at baseline and 30 days later. Of the 40000 first-year high school students aged 14-19 years 37126 (92.8%) and 865 of 900 (96.1%) academic staff agreed to take the first dose of the vaccine. The compliance rate to the second dose was 83.1% and 85% respectively. Overall two full doses have been shown to provide significant benefit which could parallel a cost-effective strategy. In conclusion school-based programs offer a good opportunity to vaccinate large number of adolescents as well as facilitate compliance with immunization schedule.