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What's new in gastroenterology and hepatology
Official reprint from UpToDate® ©2015 UpToDate®
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What's new in gastroenterology and hepatology

Disclosures: Peter A L Bonis, MD Nothing to disclose. Anne C Travis, MD, MSc, FACG, AGAF Equity Ownership/Stock Options: Proctor & Gamble [Peptic ulcer disease, esophageal reflux (omeprazole)]. Shilpa Grover, MD, MPH Nothing to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

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All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jul 2015. | This topic last updated: Aug 27, 2015.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.


Aspirin/NSAID use and risk of colorectal cancer by genotype (March 2015)

It has been unclear if the effect of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) on colorectal cancer (CRC) risk varies by genotype. In a case control study that included 8634 cases and 8553 controls pooled from 10 observational studies, regular use of aspirin, NSAIDs, or both was associated with a decreased risk of CRC [1]. Among individuals with the single-nucleotide polymorphism (SNP) rs2965667-TT genotype, regular use of aspirin/NSAIDs was also associated with a decreased risk of CRC. However, among individuals with a TA or AA genotype, which constituted 4 percent of the study population, the use of aspirin/NSAIDs was associated with an increased risk of CRC. As compared with nonregular aspirin/NSAID use, regular use in individuals with rs16973225-AA genotype, but not the AC or CC genotypes, was associated with a decreased risk of CRC. Additional studies are needed to validate this gene-environment interaction and define population subgroups that can benefit from the chemopreventive effect of aspirin/NSAIDs. (See "NSAIDs (including aspirin): Role in prevention of colorectal cancer", section on 'Biologic basis'.)

American College of Gastroenterology guidelines for hereditary gastrointestinal cancer (February 2015)

In February 2015, the American College of Gastroenterology issued recommendations for genetic testing and management of hereditary gastrointestinal cancer syndromes [2]. These guidelines highlight the need for genetic evaluation for an adenomatous polyposis syndrome in individuals with >10 cumulative colorectal adenomas and evaluation of mismatch repair deficiency in all newly diagnosed colorectal cancers. (See "Familial adenomatous polyposis: Screening and management of patients and families", section on 'Genetic testing' and "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis", section on 'Diagnostic evaluation'.)


Breath test for gastroparesis (April 2015)

The spirulina 13C breath test was approved by the United States Food and Drug Administration to diagnose gastroparesis in April 2015 [3]. Approval was based on a study of 115 patients who underwent simultaneous scintigraphy and spirulina 13C breath test. At 80 percent specificity, the 13C-spirulina breath test samples (at 150 and 180 minutes) had a combined sensitivity of 89 percent for delayed gastric emptying [4]. However, additional studies are needed to validate these results before 13C breath tests can be used routinely. (See "Gastroparesis: Etiology, clinical manifestations, and diagnosis", section on 'Alternatives to scintigraphy'.)


Daclatasvir-based regimens for genotype 3 HCV infection (August 2015)

In the era of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, patients with genotype 3 infection have emerged as a difficult-to-treat population, with suboptimal sustained virologic response (SVR) rates with short courses of previously available regimens. In July 2015, the US Food and Drug Administration approved the use of the novel NS5A inhibitor daclatasvir in combination with sofosbuvir for genotype 3 HCV infection. This agent has been available in Europe and elsewhere. Daclatasvir plus sofosbuvir for 12 weeks is now our preferred regimen for genotype 3-infected patients without cirrhosis. In an open-label study that included 120 such patients, SVR rates were 96 percent with that regimen [5]. SVR rates were only 63 percent in the 32 patients with cirrhosis included in the study, although limited evidence suggests that efficacy is enhanced with the addition of ribavirin to the regimen [6,7]. Thus, daclatasvir plus sofosbuvir plus weight-based ribavirin is our preferred regimen for genotype 3-infected patients with cirrhosis; the regimen is given for 12 to 24 weeks, although the optimal duration is uncertain. Sofosbuvir plus peginterferon plus ribavirin for 12 weeks is an effective alternative for patients willing to take interferon and has more established efficacy data. (See "Treatment regimens for chronic hepatitis C virus genotypes 2 and 3", section on 'Genotype 3'.)

Direct-acting antiviral therapy for HCV in HIV-infected patients (July 2015)

Although HIV-infected patients had lower response rates to chronic hepatitis C virus (HCV) treatment with peginterferon and ribavirin compared with HIV-uninfected patients, a growing number of studies have demonstrated that HIV/HCV coinfection is not associated with worse response to direct-acting antiviral-based regimens. Most recently, the regimen of ledpasvir-sofosbuvir for 12 weeks and the regimen of the investigational NS5A inhibitor daclatasvir with sofosbuvir for 12 weeks were each reported to result in sustained virologic response (SVR) rates exceeding 90 percent among HIV/HCV coinfected patients, including those who had failed prior HCV treatment and those with cirrhosis [8,9]. The efficacy and safety in these studies are comparable to those observed among HCV monoinfected patients. Potential drug interactions with antiretroviral agents remain a major consideration when selecting HCV treatment regimens in HIV-infected patients. (See "Treatment of hepatitis C virus infection in the HIV-infected patient", section on 'Genotype 1 infection'.)

Efficacy of pentoxifylline for severe alcoholic hepatitis remains unclear (May 2015)

In untreated patients with severe alcoholic hepatitis (Maddrey discriminant function ≥32), short-term mortality rates are high (up to 45 percent at one month). Current management options include prednisolone and pentoxifylline. However, the efficacy of pentoxifylline is unclear. The STOPAH trial is the largest trial to date to compare treatments for severe alcoholic hepatitis [10]. It included 1103 patients who were treated with prednisolone, pentoxifylline, both drugs, or neither drug. A trend toward a survival benefit was seen in patients who received prednisolone, but not in those who received pentoxifylline. However, the trial excluded sicker patients, including those with renal failure that did not stabilize within the first seven days, and the mortality rate in the placebo arm (17 percent) was lower than seen in other trials. This raises the possibility that the patients included in the trial were not representative of patients with severe alcoholic hepatitis in general. As a result, the efficacy of pentoxifylline in patients with severe alcoholic hepatitis remains unclear. Our approach is to use prednisolone for most patients with severe alcoholic hepatitis, but to use pentoxifylline in patients who have contraindications to the use of glucocorticoids. (See "Alcoholic hepatitis: Natural history and management", section on 'Pentoxifylline'.)

Investigational fixed-dose combination therapies for chronic HCV infection (May 2015)

Drug development for chronic hepatitis C virus (HCV) infection continues at a rapid pace and is yielding new, simple, and highly effective regimens that are both interferon- and ribavirin-free. Recent studies of such regimens have demonstrated the following:

A once-daily, single-pill combination of the NS3/4A protease inhibitor grazoprevir and the NS5A inhibitor elbasvir given for 12 weeks resulted in sustained virological response (SVR) rates greater than 90 percent among treatment-naïve and experienced genotype 1-infected patients with and without cirrhosis [11-13]. The addition of ribavirin to the regimen did not appear to substantially improve outcomes. Data on this regimen in patients with HIV coinfection, Child-Pugh Class B cirrhosis, severe renal impairment, and genotype 4 or 6 infection are also very promising [14-16]. This regimen is not expected to be available until 2016. (See "Investigational therapies for hepatitis C virus infection", section on 'Grazoprevir and elbasvir'.)

A single-pill combination of the NS5A inhibitor daclatasvir, the NS3/4A protease inhibitor asunaprevir, and the non-nucleoside NS5B inhibitor beclabuvir given twice daily for 12 weeks resulted in SVR rates of 92 and 89 percent among treatment-naïve and experienced genotype 1-infected patients without cirrhosis [17]. A trial among patients with cirrhosis suggested that response rates are even higher when this regimen is combined with ribavirin [18]. (See "Investigational therapies for hepatitis C virus infection", section on 'Daclatasvir and asunaprevir combinations'.)

Diagnostic criteria for hepatorenal syndrome (April 2015)

The International Club of Ascites has altered their diagnostic criteria for hepatorenal syndrome [19]. The new criteria recognize that, in such patients, acute kidney injury can sometimes be characterized by small absolute increases in serum creatinine. (See "Hepatorenal syndrome", section on 'Diagnosis'.)

Increased mortality with delayed treatment for spontaneous bacterial peritonitis (April 2015)

Patients with spontaneous bacterial peritonitis (SBP) who develop septic shock have high mortality rates, but early initiation of antimicrobial therapy may result in improved outcomes. In a retrospective study of patients with cirrhosis and SBP-associated septic shock, the risk of mortality nearly doubled (1.9-fold increase) with every hour delay in administering antimicrobial therapy [20]. In patients with suspected SBP-associated sepsis, ascitic fluid cultures should be obtained immediately and empiric antimicrobial therapy initiated to maximize the patient's chance of survival. (See "Spontaneous bacterial peritonitis in adults: Treatment and prophylaxis", section on 'Prognosis'.)

New ALBI model to assess liver function in patients with HCC (March 2015)

Hepatocellular carcinoma (HCC) is a complex disease that most often arises on a background of chronic liver disease. The complex interplay between the tumor and liver function influences prognosis, and liver function is an important consideration in treatment selection. The most commonly used model to assess severity of liver function (the Child-Turcotte-Pugh [CP] score), has never been validated in patients with HCC. A new model based upon serum albumin and bilirubin alone (the ALBI score) provides a simple, objective, and more discriminatory method of assessing liver function in patients with HCC than does the CP score; it was validated in geographically distinct cohorts of patients undergoing a range of treatments, including surgery for localized HCC and sorafenib for advanced disease [21]. The objective nature and simplicity of ALBI may diminish interobserver variation (as occurs with grading of ascites and encephalopathy in the CP scoring system) and help to refine prognostic estimates in patients treated for HCC, particularly among those with better liver function. (See "Staging and prognostic factors in hepatocellular carcinoma", section on 'ALBI score'.)

Resolution of hepatorenal syndrome after liver transplantation (March 2015)

Resolution of type 1 hepatorenal syndrome was examined in 62 patients undergoing liver transplantation at a single center over a 10 year period [22]. Of these, resolution of hepatorenal syndrome occurred in 47 patients (76 percent). The remaining patients either died or required long-term dialysis. The mean duration of dialysis prior to liver transplantation was the only significant predictor of resolution (10 days among those who resolved versus 25 days among those who did not). (See "Hepatorenal syndrome", section on 'Improving hepatic function'.)

Aminotransferase levels predict relapse in autoimmune hepatitis (February 2015)

Patients with autoimmune hepatitis who achieve remission with immunosuppressive therapy have a 50 to 90 percent chance of relapsing within 12 months if immunosuppression is withdrawn. Alanine aminotransferase (ALT) levels prior to drug withdrawal may predict which patients are more likely to achieve long-term remission. This was examined in a series of 28 patients who had been in remission with normal ALT levels for at least 24 months prior to drug withdrawal [23]. Of the 15 patients who achieved long-term remission, all had ALT levels that were <2 times the upper limit of normal at the time of drug withdrawal, whereas among the 13 who relapsed, only three had ALT levels <2 times the upper limit of normal. This study may help further guide decisions about drug withdrawal in patients with autoimmune hepatitis who are in remission. (See "Autoimmune hepatitis: Treatment", section on 'Patients in remission'.)

Interferon-free regimens to treat HCV in HIV/HCV coinfected patients (February 2015)

Patients coinfected with HIV and hepatitis C virus (HCV) traditionally had lower response rates to HCV treatment with peginterferon and ribavirin compared with individuals without HIV infection. However, with the use of direct-acting antiviral (DAA) agents in HCV treatment, HIV infection is no longer a negative predictor of response. In two studies of HIV/HCV genotype 1 coinfected individuals, sustained virological response rates to two interferon-free DAA regimens (ledipasvir-sofosbuvir or ombitasvir-paritaprevir-ritonavir and dasabuvir plus ribavirin) were greater than 90 percent, comparable to rates in populations infected with HCV alone [24,25]. The major consideration in HCV antiviral regimen selection for HIV/HCV coinfected patients is the potential for drug interactions between antiretroviral and HCV antiviral agents. (See "Treatment of hepatitis C virus infection in the HIV-infected patient", section on 'Genotype 1 infection'.)


Pentoxifylline in severe acute pancreatitis (August 2015)

Severe acute pancreatitis has a high mortality rate. In a randomized trial, 28 patients with predicted severe acute pancreatitis were assigned to pentoxifylline or placebo within 72 hours of diagnosis [26]. Patients treated with pentoxifylline had fewer intensive care unit admissions and hospital stays longer than four days as compared with placebo. However, there were no significant differences in the levels of inflammatory markers between the two groups. Studies are needed to validate these results and define the role of pentoxifylline in the treatment of acute pancreatitis. (See "Management of acute pancreatitis", section on 'Other'.)

International consensus on management of IgG4-related disease (July 2015)

The optimal treatment for immunoglobulin G4-related disease (IgG4-RD) has not been established, nor have randomized trials been performed to inform treatment approaches. Nonetheless, broad international consensus has been achieved among experts on several major management strategies [27]. These include the importance of biopsy confirmation of the diagnosis to exclude malignancy and other disorders that may mimic IgG4-RD; the need to treat symptomatic patients, sometimes urgently, as well as some asymptomatic patients; use of glucocorticoids as first-line therapy; use of maintenance therapy in certain patients; and retreatment strategies for patients who relapse after successful remission induction. Consensus was not reached on the use of steroid-sparing immunosuppressive agents from the start of treatment, and largely reflects different practice styles between countries. (See "Overview of IgG4-related disease", section on 'Diagnostic studies' and "Overview of IgG4-related disease", section on 'Treatment principles and observations'.)


Curcumin for induction of remission in ulcerative colitis (July 2015)

Curcumin is an investigational agent that may have a protective role in ulcerative colitis through modulation of the release of tumor necrosis factor-alpha and nitric oxide. In a randomized trial, 50 patients with active mild to moderate ulcerative colitis who did not respond to two weeks of maximum-dose oral and topical mesalamine therapy were assigned to additional treatment with curcumin or placebo for one month [28]. At four weeks, patients in the curcumin group had significantly higher rates of clinical and endoscopic remission as compared with the placebo group. However, curcumin can alter the stool color in some patients, and the exceptionally low response rates in the placebo group (ie, none responded) raise concern that blinding was not adequate. Additional studies are needed to support the use of curcumin in patients with ulcerative colitis. (See "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis", section on 'Curcumin'.)

Larazotide for persistent symptoms of celiac disease (June 2015)

A significant proportion of patients with celiac disease have persistent symptoms due to inadvertent gluten exposure. Larazotide acetate is an investigational oral peptide that modulates intestinal tight junctions. In a randomized trial, 342 adults with celiac disease on a gluten-free diet were assigned to three different doses of larazotide or placebo for 12 weeks to relieve ongoing symptoms [29]. The lowest dose was effective in reducing Celiac Disease Gastrointestinal Symptom Rating Scale scores (the primary endpoint), as well as reducing the number of symptomatic days, severity of abdominal pain, and related nongastrointestinal symptoms, and was well tolerated. Additional studies are needed to confirm these findings and determine optimal dosing. (See "Management of celiac disease in adults", section on 'Poor compliance or inadvertent gluten ingestion'.)

Mongersen for the treatment of active Crohn disease (March 2015)

Antisense oligonucleotides are nucleic acid sequences that bind to RNA or DNA with a high degree of specificity and can thereby block expression of a specific protein. A randomized phase 2 trial evaluated the efficacy of mongersen, an investigational oral SMAD7 antisense oligonucleotide, for the treatment of active Crohn disease. In this randomized trial, 166 patients were assigned to receive three different doses of mongersen or placebo daily for two weeks [30]. The primary outcomes were clinical remission at day 15, defined as a Crohn Disease Activity Index (CDAI) score <150, with maintenance of remission for at least two weeks, and the safety of mongersen treatment. Clinical remission rates were significantly greater in patients treated with higher doses of mongersen as compared with placebo. Clinical response rates were greater among patients receiving mongersen at any dose as compared with placebo. Most adverse events were related to complications and symptoms of Crohn disease. However, inclusion in the study was based on CDAI scores at baseline and not endoscopic confirmation of active Crohn disease. Additional studies are needed to confirm these findings and define the role of mongersen in the treatment of Crohn disease. (See "Investigational therapies in the medical management of Crohn disease", section on 'Antisense oligonucleotides'.)

Accelerated infliximab induction in patients with acute severe ulcerative colitis (February 2015)

The optimal infliximab regimen for induction of remission in acute severe ulcerative colitis (UC) is not known. A retrospective study of 50 hospitalized patients with steroid-refractory acute severe UC compared colectomy rates with standard infliximab dosing compared with an accelerated dosing regimen consisting of three induction doses of infliximab within a median period of 24 days [31]. Although colectomy rates during induction therapy were significantly lower with the accelerated regimen, there were no significant differences in colectomy rates between the groups during the following two years. Thus, additional studies are needed to identify the optimal anti-TNF dosing for the induction and maintenance of remission in patients with severe UC with the goal of decreasing the need for colectomy. (See "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis", section on 'Steroid-refractory ulcerative colitis'.)

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