Ankur Jindal

APASL consensus statements and recommendation on treatment of hepatitis C

The Asian-Pacific Association for the Study of the Liver (APASL) convened an international working party on the “APASL consensus statements and recommendation on management of hepatitis C” in March, 2015, in order to revise “APASL consensus statements and management algorithms for hepatitis C virus infection (Hepatol Int 6:409–435, 2012)”. The working party consisted of expert hepatologists from the Asian-Pacific region gathered at Istanbul Congress Center, Istanbul, Turkey on 13 March 2015. New data were presented, discussed and debated to draft a revision. Participants of the consensus meeting assessed the quality of cited studies. Finalized recommendations on treatment of hepatitis C are presented in this review.

Management of acute hepatitis B and reactivation of hepatitis B

The natural course of hepatitis B virus infection and the resulting hepatic injury is determined by the degree of virus replication and the intensity of host immune response. Upon exposure to hepatitis B virus (HBV), individuals with a vigorous and broad immune response develop acute self‐limited infection, which may result in acute hepatitis. However, with stringent testing for HBV and universal precautions, acute HBV is rather rare. Reactivation of HBV most often presents as acute hepatitis B (AVH‐B) and clinically, it is difficult to differentiate AVH‐B from reactivation of chronic hepatitis B (CHB) and it requires a high index of suspicion. In the presence of high HBV DNA (>2 × 104 IU/ml) underlying liver disease should be investigated by liver biopsy, endoscopy and/or imaging. The degree of liver failure often depends on the severity of acute insult and the stage of underlying chronic liver disease. Mutations in the HBV genome, immunosuppressive therapy and viral or drug induced injury are common causes of reactivation. As most patients with AVH‐B resolve the infection spontaneously, antiviral therapy is not indicated in them. However, the use of a potent oral nucleoside(tide) analogue is necessary as soon as possible in patients with CHB reactivation. Liver transplantation should be considered in patients who develop liver failure secondary to severe acute exacerbation. If this is not feasible, supportive therapy with the addition of granulocyte colony stimulating factor (GCSF) therapy could be beneficial.

Evaluation of acute kidney injury and its response to terlipressin in patients with acute-on-chronic liver failure

Patients with acute‐on‐chronic liver failure (ACLF) have high mortality. Cirrhotics with acute kidney injury (AKI) have poor outcome but relevance of AKI and response to terlipressin in ACLF is not known.

A randomized open label study of 'imipenem vs. cefepime' in spontaneous bacterial peritonitis.

Spontaneous bacterial peritonitis (SBP), in the presence of bacterial resistance or failure of third generation cephalosporins (3rd GC) has poor outcome. Empirical antibiotic(s) options are limited in these scenarios.

Reviewing the diagnostic criteria for acute-on-chronic liver failure

ABSTRACT Introduction: For over 20 years, acute-on-chronic liver failure (ACLF) has taken multiple definitions and/or classifications. The definition outlines the acute and chronic insults to include a homogenous patient group with liver failure and an expected outcome in a specific time frame. Early and accurate diagnosis is essential as this inflammation of the liver may tilt the balance of liver destruction and regeneration adversely. Various factors such as superadded systemic sepsis, liver reserve, cause of primary chronic liver disease, state of immune system or the state of gut microbial flora might determine the ultimate prognosis. Areas covered: To date, there has been no universally accepted definition of ACLF. In this review, we discuss the strengths and weaknesses, controversies and basis for early identification and accurate diagnosis of ACLF. PubMed and Google scholar database searches were conducted, search terms included ‘acute on chronic liver failure,’ ‘ACLF,’ and ‘diagnostic criteria.’ Expert commentary: With recent advances in the management of advanced cirrhosis, research will gradually shift towards ACLF in the near future, focusing on the pathogenesis, new treatment options and improving survival. Once we improve understanding of this syndrome, newer definitions will evolve, thereby enabling earlier diagnosis and novel therapeutic avenues.

Hepatitis B-positive health-care workers: why they should not switch to non-exposure-prone jobs

Presence of hepatitis B (HBV) infection alone should not deny a health-care professional to practice clinical medicine. No current global or regional guidelines recommend the absolute prohibition of exposure-prone invasive medical, surgical or dental procedures or practices by eligible health-care professionals, unless HBV infection is left unmonitored [1–3]. The hepatitis B prevalence in healthcare workers (HCWs) has been steadily declining globally and is likely comparable to general population. There is a wide variation in the regional or national prevalence of HBV infection among HCWs worldwide. Several authors have reported it to range from 10% in 1992 to 1% in 2008 [4, 5]. Despite this, HBV-infected HCWs represent a potential risk to their patients and the transmission of HBV from HCWs to patients has been well documented [6] [7]. Patient to HCW transmission of HBV is high [8] (30% in HBeAg ? , * 6% in HBeAg—after a single needlestick injury). Most reports occurred before widespread awareness of the risks of transmission of blood-borne pathogens in health-care settings. Worldwide implementation of HBV vaccination in infancy, catch up vaccination in adolescence, mandatory pre-employment vaccination for exposure-prone health-care professionals and adoption of standard universal precautions has largely eliminated HBV transmission risk [1]. Increasing awareness of transmission risks (mainly needle-stick injuries) and modifications in health-care practices in the last 10–20 years has also played a vital role in reducing parenteral exposure risks in health-care settings. Safeguard interventions to reduce risk of parenteral exposures have been put in place in almost all health-care institutes. In 1995, the CDC introduced the concept of ‘‘standard precautions’’ [9]. Its core elements include (1) hand disinfection after contact with patients; (2) use of barrier precautions (gloves), and minimal manipulation; (3) safe disposal of sharp instruments. It is well established that HBV transmission is extremely rare from infected health-care professionals performing minimally invasive non-exposure-prone procedures (EPP) and, therefore, these infected individuals should not be discriminated for patient care activities. Most often reason of transmission in these HCWs, if ever, is due to breach in practice of universal standard infection control. However, hepatitis B-infected health-care workers performing EPP require regular testing for HBV DNA at least 6 monthly [8]. EPP are those in which there is a risk that injury to the HCW could result in exposure of the patient’s open tissue to blood of HCW placing the patient at risk. Not only surgeons, gynecologists and dentists involved in EPP, but also other infected HCWs such as midwives and technicians who assist in EPP should be routinely tested. Factors associated with the risk of HBV transmission from HCWs to patient include serum HBV DNA level, HBeAg positivity, duration of surgery, route of transmission: percutaneous vs. mucosal and skill and medical condition of HCW [10]. The ideal cut-off of HBV DNA beyond which risk of transmission is substantially high is unknown. Current guidelines suggest variable HBV DNA cut-off limit (European guidelines, HBV DNA[ 10 IU/ml; UK guidelines, HBeAg ? or HBV DNA[ 10 IU/ml) [11]. Considering the variable spontaneous viral load fluctuations, health-care workers performing exposure-prone procedures should be treated if HBV DNA is[ 1000–2000 IU/ml. Transmission of HBV is extremely rare from HCWs with low viral loads. Many of the HCWs, therefore, may require therapy despite no absolute treatment indication otherwise. Aim of starting antivirals in this scenario is to reduce iatrogenic transmission of HBV. No prospective randomized study is available to show the safety and efficacy of antiviral agents for preventing HBV transmission by health-care workers. The end-point of treatment and follow-up duration are also unknown. Most HCWs can achieve a reduction of HBV levels to less & Ankur Jindal ankur.jindal3@gmail.com

Response to Treatment of spontaneous bacterial peritonitis: beyond the current international guidelines.

To the Editor: We agree with Fiore et al. and their concerns about the appropriate treatment protocol in spontaneous bacterial peritonitis (SBP). With implications for increased mortality because of inappropriate empirical antibiotic therapy, predictors of antibiotic resistance should be considered at baseline (1). Since markedly different epidemiological pattern of multidrug resistant (MDR) bacteria are observed even among hospitals, choice of an ideal antibiotic is difficult. Moreover, well-conducted studies have suggested that factors related to host condition are what really determine mortality (2, 3). Poor prognosis in these patients may be related to a greater severity of the underlying liver disease, higher prevalence of septic shock besides delayed initiation of appropriate antibiotics per se. Carbapenems are often considered antibiotic of choice for serious infections caused by Extended Spectrum Beta-Lactamase (ESBL) producing MDR organisms. Therefore, we also opted for carbepenem in our ‘difficult to treat’ SBP patients. Recent concerns about increasing consumption of carbapenems globally and reports of carbapenemase-producing organisms rampant in many areas had made us think of alternative options. Although, carbepenem remained the first line option, we explored non-carbepenem b-lactams that may retain activity against many ESBL-producing organisms (such as cefepime, cefamycins, b-lactum/blactum inhibitors) (4). The aim was to reduce the treatment cost and carbapenemase-producing strains. Higher dose of cefepime (2 g every 12 h) was used in order to obtain optimal drug target attainment and possibly better clinical outcomes (5). In the patients with difficult to treat SBP, both cefepime and cabepenams were of comparable and moderate efficacy. They failed to reduce mortality (almost 40% deaths at 3 months) and liver-related complications. While our study adds new data in this important field, it poses challenges to develop new techniques for rapid diagnosis of the infections in the ascitic fluid. Further, our study is a reminder that we are far from having ideal antibiotic protocols in these ‘difficult to treat’ SBP patients. As of now, physicians should be vigilant and be prepared to escalate therapy if the patient’s clinical condition deteriorates or the response tap at 48 h shows partial and non-response. There is an urgent need for clinical trials involving new antibiotics, combination of antibiotics or controlling sepsis via gut modulation or immune-based therapies.