Smruti R. Mohanty

Nonalcoholic Fatty Liver Disease: A Review and Update

The spectrum of nonalcoholic fatty liver disease (NAFLD) ranges from asymptomatic steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Hepatic steatosis occurs when free fatty acids, released in the setting of insulin resistance and the metabolic syndrome, are taken up by the liver. Additional biochemical insults, including oxidative stress, upregulation of inflammatory mediators, and dysregulated apoptosis, can result in inflammation (producing NASH) and fibrosis. Noninvasive methods (e.g., abdominal ultrasonography) are safe ways to support a diagnosis of hepatic steatosis, but advanced liver histopathologic findings including NASH and fibrosis cannot be identified without pursuing liver biopsy. Recent advances in serologic and imaging methods aim to determine severity of inflammation and fibrosis noninvasively. Currently, therapeutic options for NAFLD are limited to medications that reduce risk factors, but the future holds promise for therapies that might slow the progression of this increasingly prevalent disorder.

Predictive value of ALT levels for non-alcoholic steatohepatitis (NASH) and advanced fibrosis in non-alcoholic fatty liver disease (NAFLD).

Non‐alcoholic fatty liver disease (NAFLD) patients with elevated serum alanine aminotransferase (ALT) generally undergo a liver biopsy to evaluate for possible non‐alcoholic steatohepatitis (NASH) or advanced fibrosis. However, patients with normal ALT could also have advanced stages of NAFLD.

Influence of ethnicity on histological differences in non-alcoholic fatty liver disease

BACKGROUND/AIMS Previous studies examining ethnic differences in non-alcoholic fatty liver disease (NAFLD) are limited by small sample sizes and the lack of liver biopsy as a diagnostic modality. METHODS We retrospectively examined the influence of ethnicity on the biochemical and liver histological differences in NAFLD patients. RESULTS The proportion of African Americans (AA) in the NAFLD sample (total 238 patients; 15.1% AA) was lower than in the base population (68.2%). Median ALT (47 IU/L; p=0.05) and triglyceride (134mg/dL, p=0.002) levels were lower in AA than other ethnicities. AA showed lower degrees of steatosis [odds ratio (OR) 0.44, 95% confidence interval (CI) 0.22-0.89; p=0.02] than Whites. In contrast, Asians showed higher grades of ballooning than Whites (OR 2.67, 95% CI 1.03-6.93; p=0.04) and other ethnicities combined (OR 2.71, 95% CI 1.06-6.92; p=0.04). Hispanics showed a higher rate of Mallory bodies than Whites (OR 2.38, 95% CI 1.05-5.39; p=0.04) and other ethnicities combined (OR 2.41, 95% CI 1.09-5.34; p=0.03). CONCLUSIONS African Americans showed a lower degree of steatosis than Whites. In contrast, Asians and Hispanics showed higher grades of ballooning and Mallory bodies, respectively, than Whites and other ethnicities combined. These findings highlight the need for prospective studies to evaluate ethnic differences in NAFLD.

Improving the quality of colonoscopy bowel preparation using an educational video

Colonoscopy is the preferred modality for colon cancer screening. A successful colonoscopy requires proper bowel preparation. Adequate bowel preparation continues to remain a limiting factor. One hundred thirty-three patients scheduled for an outpatient colonoscopy were prospectively randomized in a single-blinded manner to video or nonvideo group. In addition to written bowel preparation instructions, patients in the video group viewed a brief instructional video. Quality of colon preparation was measured using the Ottawa Bowel Preparation Quality scale, while patient satisfaction with preparation was evaluated using a questionnaire. Statistical analyses were used to evaluate the impact of the instructional colonoscopy video. There were significant differences in the quality of colonoscopy preparation between the video and the nonvideo groups. Participants who watched the video had better preparation scores in the right colon (P=0.0029), mid-colon (P=0.0027), rectosigmoid (P=0.0008), fluid content (P=0.03) and aggregate score (median score 4 versus 5; P=0.0002). There was no difference between the two groups with regard to patient satisfaction. Income, education level, sex, age and family history of colon cancer had no impact on quality of colonoscopy preparation or patient satisfaction. The addition of an instructional bowel preparation video significantly improved the quality of colon preparation.

Treatment of chronic hepatitis B.

Treatment of chronic hepatitis B has improved substantially over the past five years. Pegylated interferon α2a and entecavir have been approved by the FDA and joined the armamentarium of therapies that includes inteferon α (IFN-α), lamivudine, and adefovir dipivoxil. Several key questions come to mind regarding treatment. Who should receive treatment? Which agent should they be given? How long should treatment last? Treatment is indicated for patients with a high pretreatment alanine aminotransferase level, detectable HBV DNA, and active inflammation on liver biopsy. When selecting an agent, the likelihood of achieving a sustained response should be weighed against long-term risks. IFN-α, lamivudine, and adefovir dipivoxil are equally efficacious; however, even though IFN-α and pegylated IFN-α have a durable response, both are associated with unpleasant side effects. Long-term lamivudine therapy has a high rate of drug resistance compared with adefovir dipivoxil, which has a low rate of drug resistance and a small risk of reversible nephrotoxicity. Entecavir reduces HBV load more effectively than the other therapies, but it is associated with increased drug resistance in patients with lamivudine-resistant HBV. The key to therapy seems to be some combination of therapies—both existing and those in development—that has yet to be determined.

Prevalence of Helicobacter pylori infection in bariatric patients: a histologic assessment

BACKGROUND Studies on rates of Helicobacter pylori (HP) infection in morbidly obese patients awaiting bariatric surgery are conflicting because of small sample size and variability in diagnostic testing. The objective of this study was to determine the rate of biopsy-proven active HP infection in morbidly obese patients undergoing bariatric surgery. METHODS Retrospective analysis was done on all morbidly obese patients who underwent bariatric surgery between 2001 and 2009. All patients underwent preoperative upper endoscopy with biopsy to evaluate HP status. All endoscopies and surgeries were performed by a single endoscopist and surgeon, respectively. Data were analyzed with Student t test, Pearson χ(2) test, and logistic regression for multivariate analysis. RESULTS The 611 patients included 79 males (12.9%) and 532 females (87.1%). Mean age was 39.9 ± 10.7 years, and mean body mass index (BMI) was 47.8 ± 6.4 kg/m(2). The overall HP infection rate was 23.7%. Rate of infection did not differ between gender (22.8% in males, 23.9% in females; P = .479) or BMI (48.6 ± 6.5 kg/m(2) in HP-positive patients, 47.5 ± 6.4 kg/m(2) in HP-negative patients; P = .087). Patients with HP were older compared with those without infection (41.2 versus 38.7 years; P =.016). Hispanics had a higher prevalence of HP (OR 2.35; P = .023). CONCLUSION Increasing BMI is not an independent risk factor for active HP infection within the morbidly obese patient population. Need for invasive testing to detect HP infection in these patients should be re-evaluated. Other methods of detecting active HP infection should be considered as an alternative to invasive or serologic testing.

Evaluation of Early Null Response to Pegylated Interferon and Ribavirin as a Predictor of Therapeutic Nonresponse in Patients Undergoing Treatment for Chronic Hepatitis C

OBJECTIVES:Early viral kinetics accurately predicts sustained virological response (SVR) in genotype 1 patients with hepatitis C virus (HCV) undergoing therapy with pegylated interferon (PEG) and ribavirin (RBV). No baseline factor has a stronger predictive role. Early identification of patients unlikely to respond is equally important, allowing early treatment modification or discontinuation. The aim of this study was to determine whether 4-week null response (eNR) correlates directly with 12-week null response and inversely with SVR.METHODS:A retrospective analysis of HCV patients treated at our institution was done. Patients were classified based on a 4-week viral log decline compared with baseline: <1 log, ≥1 log, <2 log, ≥2 log, <3 log, ≥3 log without rapid virological response (RVR) and with RVR. eNR was defined as less than a 1 log change from baseline.RESULTS:A total of 159 patients had quantitative HCV-RNA PCR at treatment week 4, of whom 24% (38) experienced eNR. In all, 22 (58%) of the eNR patients were African American, 58% male, 32% cirrhotic, average age 53 years (range 36–71), 89% (33) genotype 1, and average baseline viral load was 5.9261 log (range 3.1492–7.3025). On-treatment response demonstrated failure to attain early virological response (EVR; 2-log decline at week 12) in 50% (19) and partial EVR (pEVR) in 39% (15). Three (8%) patients with eNR achieved SVR. In our patient population, eNR had 92% negative predictive value (confidence interval 83.5–100%) for SVR and was the strongest single predictor for treatment failure, including the baseline factors genotype and viral load.CONCLUSIONS:eNR is strongly associated with null response or pEVR and accurately predicts failure to attain SVR. Consideration should be made to discontinue or modify therapy in patients with eNR who receive the appropriate weight-based PEG/RBV.

Persistent spontaneous bacterial peritonitis: a common complication in patients with spontaneous bacterial peritonitis and a high score in the model for end-stage liver disease

Objectives: Spontaneous bacterial peritonitis (SBP) is associated with a high mortality rate. After antibiotic therapy, improvement in fluid polymorphonuclear (PMN) cell count is expected within 2 days. However, our institution recognized cases unresponsive to standard treatment. Methods: To study these recalcitrant cases, we completed a retrospective chart review of patients admitted for SBP to the University of Chicago from 2002 to 2007. SBP was defined by an ascitic PMN cell count ≥250/ml. Results: Of 55 patients with SBP, 15 did not show improvement in fluid PMN cell count to below 250/ml with standard treatment, leading to a prevalence of 27%. The patients with persistent SBP were younger than those with nonpersistent SBP [mean (SD) 51.80 (9.84) compared with 58.13 (8.79); p = 0.0253]. Persistent SBP had a higher serum ascites albumin gradient (SAAG) [median (Q1, Q3) 1.85 (1.50, 2.41) compared with 1.10 (0.60, 1.60)] and a higher score in the model for end-stage liver disease (MELD) [mean (SD) 27.98 (8.09) compared with 22.22 (8.10)] than nonpersistent SBP patients; p = 0.027 and p = 0.023, respectively. In addition, persistent SBP patients were more likely to have a positive ascitic fluid culture than nonpersistent SBP patients [odds ratio (OR) (95% CI) 4.33 (1.21, 15.47); p = 0.024]. Importantly, in-hospital mortality in the persistent SBP group was 40%, compared with 22.5% in the nonpersistent SBP group [OR = 2.30 (0.64, 8.19); p = 0.20]. Conclusions: The risk of persistent SBP is nearly 40% in patients with MELD score >25, SAAG >1.5 or positive ascitic fluid culture. Furthermore, patients who develop persistent SBP tend to experience a higher mortality rate. This study underscores the importance of further examination of this vulnerable population.

A Comprehensive Updated Review of Pharmaceutical and Nonpharmaceutical Treatment for NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the western world with prevalence of 20–33%. NAFLD comprises a pathological spectrum. Nonalcoholic fatty liver (NAFL) is at one end and consists of simple hepatic steatosis. On the contrary, nonalcoholic steatohepatitis (NASH) consists of steatosis, inflammation, and ballooning degeneration and can progress to cirrhosis. Despite the rising incidence, definitive treatment for NAFLD, specifically NASH, has not yet been established. Lifestyle modification with dietary changes combined with regular aerobic exercise, along with multidisciplinary approach including cognitive behavior therapy, has been shown to be an effective therapeutic option, even without a significant weight loss. Pioglitazone and vitamin E have shown to be most effective in NASH patients. Surgery and weight loss medication are effective means of weight loss but can potentially worsen NASH related fibrosis. Other agents such as n-3 polyunsaturated fatty acids, probiotics, and pentoxifylline along with herbal agent such as milk thistle as well as daily intake of coffee have shown potential benefits, but further well organized studies are definitely warranted. This review focuses on the available evidence on pharmaceutical and nonpharmaceutical therapy in the treatment and the prevention of NAFLD, primarily NASH.

Liver Transplantation for Disulfiram-induced Fulminant Hepatic Failure

Disulfiram has been used as a popular adjunct in programs for alcohol rehabilitation. However, in rare cases, disulfiram has been reported to cause fulminant hepatitis. Disulfiram use and its associated complications in adolescents have received minimal attention in the literature. We report the first pediatric case of successful orthotopic liver transplantation for disulfiram-induced fulminant hepatic failure in a 16-year-old girl, who developed an idiosyncratic reaction associated with short-term, low-dose disulfiram use, as evidenced by her liver biopsy and explanted liver. This case report indicates that a high index of suspicion, and aggressive therapeutic interventions are necessary to recognize and manage disulfiram-induced fulminant hepatic failure in adolescents. Success of this case suggests that transplant centers should consider liver transplantation of an adolescent alcoholic patient with fulminant hepatic failure due to non-alcohol-related causes such as disulfiram. Orthotopic liver transplantation should be considered early in the management of disulfiram-induced fulminant hepatic failure.