Sudha Kodali

Unusually High Rates of Hepatocellular Carcinoma After Treatment With Direct-Acting Antiviral Therapy for Hepatitis C Related Cirrhosis

Dear Editors: Direct-acting antiviral (DAA) therapy has revolutionized the treatment of hepatitis C virus (HCV) infection, with very high rates of sustained virologic response (SVR) and an excellent safety profile. Interferon-based therapies in the past have shown improved outcomes, including reduced risk for occurrence and recurrence of hepatocellular carcinoma (HCC) with the achievement of SVR. However, data on the impact of DAA therapy on the natural history and development of HCC are limited. Recently, studies have shown unexpected high HCC recurrence rate of 27%-29% among patients treated with resection or ablation, who received DAA therapy. However, similar results were not reproduced in analyses of three prospective cohorts from France. Among patients with HCV-related cirrhosis without prior history of HCC, DAA treatment was not associated with reduction in the occurrence of HCC. In one of these studies, de novo occurrence of HCCwas reported at rate of 3.17%within 6months of completing DAA therapy for HCV infection. With scanty and conflicting data on the association of HCC with DAA therapy, we performed this retrospective study to examine occurrence of de novo HCC among HCV-infected patients with cirrhosis during or after treatment with DAA.

ERCP-related perforations in the new millennium: A large tertiary referral center 10-year experience.

Introduction Endoscopic retrograde cholangiopancreatography (ERCP) is an important diagnostic and therapeutic modality for pancreatic and biliary disorders. Perforation is one of the most dreaded complications of ERCP. Since it is uncommon, there has been little study of incidence, risk factors, and outcomes of management. Objectives We aim to assess the incidence of ERCP-related perforations and outcomes at a large tertiary referral center. Methods We undertook a review of an ERCP database for all perforations from 2002 to December 2012. Results The cumulative incidence of ERCP-related perforations was 0.14% (12 out of 8264), and sphincterotomy-related perforations constituted the most common cause. The mean age of these 12 patients was 58.6 years and majority were female (83.3%). The most common indications for ERCP were: suspected sphincter of Oddi dysfunction (SOD) 41%, and common bile duct stones (CBD stones) 41%. Nine of the 12 patients (75%) had a leak and were managed medically, and four who had a perforation had surgical repair (25%). Conclusions In our study, leaks were much more common than perforations and the majority of patients were successfully managed with conservative therapy alone. We report a very low perforation rate and most perforations can be managed conservatively with a good outcome.

Diagnosis and Treatment of Alcoholic Hepatitis: A Systematic Review

Alcoholic hepatitis (AH) occurs in about one-third of individuals reporting long-term heavy alcohol use. It is associated with high short-term mortality, economic burden, and hospital resources utilization. We performed this systematic review to (i) describe clinical characteristics and genomics associated with the risk of AH; (ii) discuss role and limitations of liver biopsy and prognostic scoring systems; (iii) summarize evidence regarding the currently available therapies including liver transplantation; and (iv) outline emerging therapies with areas of unmet need. Literature search was performed for studies published in English language (January 1971 through March 2016). The following search engines were used: PubMed, Elsevier Embase, PsycINFO, and Cochrane Library. For the treatment section, only randomized controlled studies were included for this review. A total of 138 studies (59 randomized, 22 systematic reviews or meta-analyses, 7 surveys or guidelines, 7 population-based, and 43 prospective cohorts) were cited. There are over 325,000 annual admissions with AH contributing to about 0.8% of all hospitalizations in the United States. Liver biopsy may be required in about 25 to 30% cases for uncertain clinical diagnosis. Corticosteroids with or without N-acetylcysteine remains the only available therapy for severe episodes. Data are emerging on the role of liver transplantation as salvage therapy for select patients. Abstinence remains the most important factor impacting long-term prognosis. Results from the ongoing clinical trials within the National Institute on Alcohol Abuse and Alcoholism-funded consortia are awaited for more effective and safer therapies. AH is a potentially lethal condition with a significant short-term mortality. A high index of suspicion is required. There remains an unmet need for noninvasive biomarkers for the diagnosis, and predicting prognosis and response to therapy.

Diagnosis and Management of Hepatic Encephalopathy in Fulminant Hepatic Failure

Hepatic encephalopathy (HE) is associated with cerebral edema (CE), increased intracranial pressure (ICP), and subsequent neurologic complications; it is the most important cause of morbidity and mortality in fulminant hepatic failure. The goal of therapy should be early diagnosis and treatment of HE with measures to reduce CE. A combination of clinical examination and diagnostic modalities can aid in prompt diagnosis. ICP monitoring and transcranial Doppler help diagnose and monitor response to treatment. Transfer to a transplant center and intensive care unit admission with airway management and reduction of CE with hypertonic saline, mannitol, hypothermia, and sedation are recommended as a bridge to liver transplantation.

Hepatic porphyria: A narrative review

Porphyrias are a group of metabolic disorders, which result from a specific abnormality in one of the eight enzymes of the heme biosynthetic pathway. These have been subdivided based on the predominant site of enzyme defect into hepatic and erythropoietic types and based on clinical presentation into acute neurovisceral and cutaneous blistering porphyrias. This review focuses on hepatic porphyrias, which include acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), aminolevulinic acid dehydratase deficiency porphyria (ADP), and porphyria cutanea tarda (PCT). Of these, AIP and ADP are classified as acute porphyria, PCT as cutaneous, while VP and HCP present with both acute and cutaneous clinical manifestations. Porphobilinogen levels in a spot urine sample is the initial screening test for the diagnosis of acute hepatic porphyria, and plasma with spot urine porphyrin levels is the initial screening test to approach patients suspected of cutaneous porphyria. Specific biochemical porphyrin profile for each porphyria helps in determining the specific diagnosis. Pain relief and elimination of triggering agents are the initial steps in managing a patient presenting with an acute attack. Intravenous glucose administration terminates the mild episode of acute porphyria, with intravenous hemin needed for management of moderate to severe episodes. Liver transplantation is curative and may be needed for patients with a life-threatening acute porphyria attack or for patients with recurrent acute attacks refractory to prophylactic treatment. Of the cutaneous porphyrias, PCT is the most common and is frequently associated with a combination of multiple susceptibility factors such as alcohol use, smoking, hepatitis C virus infection, HIV infection, estrogen use, and mutations of the hemochromatosis gene. Regular phlebotomy schedule and low-dose hydroxychloroquine are effective and safe treatment options for management of PCT.

Alcohol Relapse After Liver Transplantation for Alcoholic Cirrhosis—Impact on Liver Graft and Patient Survival: A Meta-analysis

Aim We performed meta-analysis to determine effect of alcohol relapse after liver transplantation (LT) for alcoholic cirrhosis on graft histology and survival. Methods Studies were selected using following criteria: (a) LT for alcoholic cirrhosis, (b) reporting data on liver histology and/or patient survival among relapsers and abstainers, (c) minimum follow-up of 3 years. Random effects model was used to pool data to compare relapsers and abstainers on liver histology and patient survival. Results On analysis of seven studies, pooled prevalence of self-reported alcohol relapse was 26.3% (18.0-36.7%) over median (range) follow-up of 6.0 (3.7-8.3) years, with annual alcohol relapse rate of 4.7% (3.0-6.4%) for any alcohol use and 2.9% (0.5-5.3%) for heavy alcohol use. Relapsers compared to abstainers had higher odds for graft steatosis [4.1 (2.4-6.9)], steatohepatitis [4.5 (1.4-14.2)], alcoholic hepatitis [9.3 (1.01-85)], advanced fibrosis or cirrhosis [8.4 (3.5-20)]. Relapsers were over 3-fold more likely to die at 10 years of follow-up: [3.67 (1.42-9.50)] without differences in overall or 5-year survival. Recurrent alcoholic cirrhosis occurring in 9% of biopsied patients and 2% of all transplants was responsible for about 20% of all deaths on follow-up after LT. Extra-hepatic malignancy, and cardiovascular events were common causes for patient mortality. Conclusion Alcohol relapse after LT for alcoholic cirrhosis negatively impacts the graft and long-term patient survival. Studies are needed to develop strategies to reduce alcohol relapse after LT for alcoholic cirrhosis. Short Summary Alcohol relapse in liver transplant recipients can negatively affect graft histology and patient survival. Strategies to reduce alcohol relapse are needed to preserve graft function?

A new meaning to butterflies in the stomach.

Question: A 68-year-old woman with rheumatoid arthritis maintained on methotrexate presented with a 4-year history of intermittent episodes of abdominal pain and nausea that gradually progressed to emesis and increasing abdominal girth. The symptoms usually lasted for 48-72 hours with resolution of symptoms with food avoidance. Her symptoms initially began after starting methotrexate, which she took orally for 3 years followed by 1 year as a subcutaneous injection. The symptoms were exacerbated after each subsequent weekly dose. Her vital signs, laboratory studies, and physical examination were normal except for mild diffuse abdominal tenderness, hyperactive bowel sounds, and bulging flanks. An upper gastrointestinal series with small bowel follow through showed signs of partial small bowel obstruction. Abdominal CT revealed loculated abdominal and pelvic ascites with an associated peripheral rim enhancement (Figure A, arrow at peripheral rim enhancement). Paracentesis with analysis of peritoneal fluid revealed a transudative process. She subsequently underwent diagnostic laparotomy for persistent symptoms of suspected small bowel obstruction unresponsive to conservative measures. An unusual white encasing material around the peritoneum and small bowel wall without any strangulation or overt obstruction (Figure B, C) was noted. Peritoneal biopsy obtained at the time of the surgery contained acellular white clotted material with no findings of malignancy. What is the diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.

Text Messaging Approach Improves Weight Loss in Patients with Nonalcoholic Fatty Liver Disease: A Randomized Study

Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease. The only effective treatment is 7%‐10% weight loss. Mobile technology is increasingly used in weight management. This study was performed to evaluate the effects of text messaging intervention on weight loss in patients with NAFLD.

Potent suppression of hepatitis B virus and hepatocellular carcinoma: how long is good enough?

Approximately one third of the world’s population has serological evidence of past or present infection with hepatitis B virus (HBV). The natural history of chronic HBV infection, ranges from an inactive carrier state to progressive chronic hepatitis B (CHB), which may evolve to cirrhosis and hepatocellular carcinoma (HCC) (1,2).

Mo1022 Effect of Body Mass Index (BMI) on Functional Status of Patients With Cirrhosis Based on the Six-Minute Walk Test (6mwt)

Background & Aims: Hepatic encephalopathy (HE) represents a spectrum of neurocognitive impairment seen in cirrhotic patients and is considered to be fully reversible with treatment, however recent evidence suggests otherwise. This longitudinal study was carried out to evaluate the persistence of cognitive impairment in cirrhotics with prior overt HE (OHE) episode despite treatment. Methods: Of 213 patients screened, 107 patients who met the eligibility criteria were enrolled and 102 patients completed the study (52 patients without prior OHE episode and 50 patients with prior OHE). Among 102 patients included in the study, 86 were men and 16 were women; 67 (65.7%) patients had alcoholic etiology and 35 (34.3%) had non-alcoholic etiology (hepatitis B virus 6 patients, hepatitis C virus 4 patients, cryptogenic 14 patients, miscellaneous 11 patients). All patients underwent psychometric hepatic encephalopathy score (PHES) evaluation at 3 separate visits (Day 1, Day 3 and between 30 and 60 days, median 34). PHES ≤5 was considered abnormal and diagnostic of minimal HE (MHE). One point improvement in PHES between first and second evaluation was considered as a measure of learning. Results: Thirty-four (33.3%) of patients with cirrhosis of liver had MHE; 20 (40%) with prior episode and 14 (26.9%) without prior episode of OHE had MHE. Patients with previous OHE episode showed learning impairment in PHES on repetition on 3rd day [Day 1, mean -3.70 (95% confidence intervals -4.71 -2.68) versus Day 3, -4.02 (-5.06-2.97); P = 0.084] as compared to patients without prior OHE episode [Day 1, -2.26 (-3.13 -1.40) versus Day 3, -0.44 (-1.24 0.35); P <0.0001] irrespective of having MHE or not. In this study, 57 patients were learners, i.e., 1point improvement in PHES (55.8%) and 45 patients were non-learners (44.2%). Univariate analysis demonstrated that Child-Turcotte-Pugh score, lactulose and/or rifaximin therapy, presence of MHE and previous OHE episode were associated with learning impairment. Multivariate analysis demonstrated that only presence of previous episode of OHE (adjusted odds ratio [95%, confidence interval; 38.398, 9.192 160.4]; p <0.0001) significantly affected learning. Conclusions: This study conclusively demonstrated learning impairment in cirrhotic patients with previous episode of OHEdespite normalmental status. Improvement in PHES on repetition can be used as a measure of learning in future studies.