Ashwani K. Singal

Antiviral Therapy Reduces Risk of Hepatocellular Carcinoma in Patients With Hepatitis C Virus–Related Cirrhosis

BACKGROUND & AIMS The effects of antiviral therapy on prevention of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related cirrhosis are unclear. We performed a systematic review and meta-analysis to assess HCC risk reduction in patients with HCV-related cirrhosis who have received antiviral therapy. METHODS Twenty studies (4700 patients) were analyzed that compared untreated patients with those given interferon (IFN) alone or ribavirin. Risk ratios (RRs) determined effect size using a random effects model. RESULTS Pooled data showed reduced HCC risk in the treatment group (RR, 0.43; 95% confidence interval [CI], 0.33-0.56), although the data were heterogenous (chi(2) = 59.10). Meta-regression analysis showed that studies with follow-up durations of more than 5 years contributed to heterogeneity. Analysis of 14 studies (n = 3310) reporting sustained virologic response (SVR) rates with antiviral treatment showed reduced HCC risk in patients with an SVR, compared with nonresponders (RR, 0.35; 95% CI, 0.26-0.46); the maximum benefits were observed in patients treated with ribavirin-based regimens (RR, 0.25; 95% CI, 0.14-0.46). Meta-analysis of 4 studies assessing the role of maintenance IFN in nonresponders did not show HCC risk reduction (RR, 0.58; 95% CI, 0.33-1.03). No publication bias was detected by the Egger test analysis (P > 0.1). CONCLUSIONS The risk of HCC is reduced among patients with HCV who achieve an SVR with antiviral therapy. Maintenance therapy with IFN does not reduce HCC risk among patients who do not respond to initial therapy. View this articles video abstract atwww.cghjournal.org.

Antioxidants as therapeutic agents for liver disease.

Oxidative stress is commonly associated with a number of liver diseases and is thought to play a role in the pathogenesis of chronic hepatitis C, alcoholic liver disease, non‐alcoholic steatohepatitis (NASH), haemochromatosis and Wilsons disease. Antioxidant therapy has thus been considered to have the possibility of beneficial effects in the management of these liver diseases. Despite this promise, antioxidants have produced mixed results in a number of clinical trials of efficacy. This review summarizes the results of clinical trials of antioxidants as sole or adjuvant therapy of chronic hepatitis C, alcoholic liver disease and non‐alcoholic steatohepatitis (NASH). Overall, the most promising results to date are for vitamin E therapy of NASH but some encouraging results have been obtained with antioxidant therapy of acute alcoholic hepatitis as well. Despite evidence for small reductions of serum alanine aminotransferase, there is as yet no convincing evidence that antioxidant therapy itself is beneficial to patients with chronic hepatitis C. Problems such as small sample size, short follow up duration, inadequate endpoints, failure to demonstrate tissue delivery and antioxidant efficacy, and heterogeneous nature of the ‘antioxidant’ compounds used have complicated interpretation of results of the clinical studies. These limitations and their implications for future trial design are discussed.

Outcomes after liver transplantation for alcoholic hepatitis are similar to alcoholic cirrhosis: Exploratory analysis from the UNOS database

Data on liver transplantation for patients with alcoholic hepatitis are limited. Using the United Network for Organ Sharing database (2004‐2010), adults undergoing liver transplantation for a listing diagnosis of alcoholic hepatitis were matched for age, gender, ethnicity, and model for endstage disease (MELD) score, donor risk index, and year of transplantation with three patients transplanted for a listing diagnosis of alcoholic cirrhosis. Study outcomes of graft and patient survival on follow‐up were also analyzed for cohorts based on the diagnosis of the explant (46 alcoholic hepatitis and 138 alcoholic cirrhosis) and diagnosis at both listing as well as of the explant (11 alcoholic hepatitis and 33 alcoholic cirrhosis). Five‐year graft and patient survival of alcoholic hepatitis and alcoholic cirrhosis patients were 75% and 73% (P = 0.97) and 80% and 78% (P = 0.90), respectively. Five‐year graft and patient survival rates were also similar for cohorts based on diagnosis of the explant and diagnosis at listing as well as explant. Cox proportional regression analysis adjusting for other variables showed no impact of the etiology of liver disease (alcoholic hepatitis versus alcoholic cirrhosis) on the graft and patient survival. The causes of graft loss and patient mortality were similar in the two groups, and were not alcohol‐related in any patient. Conclusion: Compared with alcoholic cirrhosis, patients with alcoholic hepatitis have similar posttransplantation graft and patient survival. Based on these preliminary findings, liver transplantation may be considered in a select group of patients with alcoholic hepatitis who fail to improve with medical therapy. Prospective studies are needed to assess the long‐term outcome after liver transplantation in patients with alcoholic hepatitis. (HEPATOLOGY 2012)

Meta-analysis: interferon improves outcomes following ablation or resection of hepatocellular carcinoma

Aliment Pharmacol Ther 2010; 32: 851–858

The renal safety of bowel preparations for colonoscopy : a comparative study of oral sodium phosphate solution and polyethylene glycol

Background  Rare cases of nephrotoxicity have been reported with oral sodium phosphate solution (OSPS).

Low-Dose Hydroxychloroquine Is as Effective as Phlebotomy in Treatment of Patients With Porphyria Cutanea Tarda

BACKGROUND & AIMS Porphyria cutanea tarda (PCT) is an iron-related disorder caused by reduced activity of hepatic uroporphyrinogen decarboxylase; it can be treated by phlebotomy or low doses of hydroxychloroquine. We performed a prospective pilot study to compare the efficacy and safety of these therapies. METHODS We analyzed data from 48 consecutive patients with well-documented PCT to characterize susceptibility factors; patients were treated with phlebotomy (450 mL, every 2 weeks until they had serum ferritin levels of 20 ng/mL) or low-dose hydroxychloroquine (100 mg orally, twice weekly, until at least 1 month after they had normal plasma levels of porphyrin). We compared the time required to achieve a normal plasma porphyrin concentration (remission, the primary outcome) for 17 patients treated with phlebotomy and 13 treated with hydroxychloroquine. RESULTS The time to remission was a median 6.9 months for patients who received phlebotomy and 6.1 months for patients treated with hydroxychloroquine treatment (6.7 and 6.5 mo for randomized patients), a difference that was not significant (log-rank, P = .06 and P = .95, respectively). The sample size was insufficient to confirm noninferiority of hydroxychloroquine treatment (hazard ratio, 2.19; 95% confidence interval, 0.95-5.06) for all patients. Patients who received hydroxychloroquine had substantially better compliance. There were no significant side effects of either treatment. CONCLUSIONS Hydroxychloroquine, 100 mg twice weekly, is as effective and safe as phlebotomy in patients with PCT, although noninferiority was not established. Given these results, higher-dose regimens of hydroxychloroquine, which have more side effects, do not seem justified. Compliance was better and projected costs were lower for hydroxychloroquine than phlebotomy treatment. Long-term studies are needed to compare durability of response. ClinicalTrials.gov number, NCT01573754.

Impact of hepatitis C virus infection on the course and outcome of patients with acute alcoholic hepatitis

Background and aims Limited information is available on the impact of hepatitis C virus (HCV) infection on the clinical course and outcome of acute alcoholic hepatitis (AH), a condition with a significant mortality. We designed this retrospective study to assess effect of HCV on the outcome of patients with AH. Methods Medical charts of patients with a discharge diagnosis of AH (defined using rigorous clinical criteria) were reviewed. Patients were stratified based on the presence or absence of concomitant HCV infection. The disease severity was estimated at admission and at day 7 using model for end-stage disease and discriminant function index scores. Patient survival at 6 months was confirmed with the county death registry. Results A total of 76 (29 HCV positive) AH cases were analyzed. At admission, disease severity was similar in both groups with severe disease in 53% (49% of AH alone and 59% of AH+HCV; P=0.18). Although severity scores at day 7 were not available for all patients, disease severity tended to be worse for patients with AH+HCV. Kaplan–Meier survival curves showed a poor survival for AH+HCV compared with AH alone (69 vs. 91%; log-rank P=0.015). Although patients with AH+HCV were treated less often compared with AH alone (27 vs. 54%; P=0.05), HCV emerged as an independent risk factor for a poor outcome at 6 months (Cox proportional hazard ratio 8.45; P=0.01) after controlling for patient demographics, disease severity at admission, and treatment. Conclusion HCV may be a risk factor for patients with AH with a worse outcome at 6 months. If our findings are confirmed in larger databases, prospective studies are needed to examine mechanisms for this effect of HCV on the outcome of AH.

Duplex Doppler Ultrasound Examination of the Portal Venous System: An Emerging Novel Technique for the Estimation of Portal Vein Pressure

PurposeMeasurement of portal venous pressure in patients with portal hypertension is important to assess efficacy of beta blockers in patients with esophageal varices. Currently, the gold standard for measurement of portal venous pressure is the estimation of hepatic venous pressure gradient (HVPG). Being an invasive technique, serial measurements of HVPG are not feasible in clinical practice. In this respect, duplex Doppler ultrasound (DDUS) examination is an upcoming non-invasive technique for the estimation of portal venous and splanchnic hemodynamics. The aim of the present review is to analyze the current literature focusing on how the two techniques compare to each other in terms of assessing the portal pressure and assessing pitfalls in the current technique.ResultsDuplex Doppler ultrasound (DDUS) currently has limitations in measuring the portal pressure in a non-invasive way. Hemodynamic venous and arterial indices measured on DDUS correlate with the HVPG. The technique has been refined, however, there is no uniform surrogate marker that can be used in clinical practice.ConclusionsMore studies are needed in order to remove the shortcomings in the current technique. The target is to be able to measure the actual portal pressure or at least derive an ideal venous or arterial hemodynamic surrogate marker having close correlation with the HVPG.

Outcome After Liver Transplantation for Cirrhosis Due to Alcohol and Hepatitis C: Comparison to Alcoholic Cirrhosis and Hepatitis C Cirrhosis

Background and Aim: Data on outcome of patients after liver transplantation (LT) for cirrhosis due to hepatitis C virus (HCV+) alcohol are limited. Methods and Results: Analysis from United Network for Organ sharing data set (1991 to 2010) for cirrhotics with first LT for HCV (group I, N=17,722), alcohol or alcoholic cirrhosis (AC; group II, N=9617), and alcohol+HCV (group III, N=6822). Five-year graft and patient survival for group III were similar to group I (73% vs. 69%; P=0.33 and 76% vs. 76%; P=0.87) and worse than group II (70% vs. 74%; P<0.0001 and 76% vs. 79%; P<0.0001). Cox regression analysis adjusted for recipient and donor characteristics showed (a) graft survival for group III similar to group I [hazard ratio (HR) 1.03 (95% confidence interval (CI), 0.97-1.09)] and worse than group II [HR 1.27 (95% CI, 1.19-1.35)] and (b) patient survival for group III worse than both groups I [HR 1.09 (95% CI, 1.02-1.15)] and II [HR 1.27 (95% CI, 1.19-1.36)]. In group III, graft failure was common for graft and patient loss and de novo malignancy more common compared with group I. Conclusions: Patients undergoing LT for cirrhosis due to combined alcohol and HCV have (a) graft survival similar to patients with HCV cirrhosis and worse than AC and (b) worse patient survival compared with AC and HCV cirrhosis. Better strategies for anti-HCV treatment and screening for tumors are needed for patients undergoing LT for combined alcohol and HCV.

Ulcers After Intravariceal Sclerotherapy: Correlation of Symptoms and Factors Affecting Healing

Esophageal variceal ulcers have been held responsible for most postsclerotherapy complaints. To investigate a possible relation between these ulcers and symptoms, we followed for 4 weeks 40 patients with portal hypertension who had received a single course of intravariceal sclerotherapy. All 40 patients were found to have mucosal variceal ulcers on the day after sclerotherapy. One or more symptoms were given by 26 (65%) patients; dysphagia by 53% (mean duration 4.6 +/- 2.2 days), retrosternal pain by 28% (mean duration 3.0 +/- 2.5 days), and fever by 15% (mean duration 2.1 +/- 0.4 days). A gastric variceal ulcer was responsible for bleeding in one (2.2%) patient. We found no correlation between the occurrence and duration of symptoms and the presence of variceal ulcers. While symptoms were transient, ulcers persisted for several days to weeks in most patients. Patients who had received a higher amount of sclerosant developed larger ulcers (greater than 1 cm) with more symptoms and healing was more delayed than in those who had received lesser amounts and developed smaller ulcers (less than 1 cm). In patients with a serum albumin level greater than 3.0 g/dl, ulcers healed more often than in those with a less than 3.0 g/dl albumin (72 versus 18%, p less than 0.05). Development of mucosal ulcers is a natural consequence of intravariceal sclerotherapy and it appears unrelated to symptoms. The chemical nature and the volume of the injected sclerosant are probably responsible for the symptoms after sclerotherapy. Further, postsclerotherapy ulcers heal spontaneously, more often in patients with good nutritional status.