Anurag Maheshwari

Acute hepatitis C

Symptomatic acute hepatitis C occurs in only about 15% of patients who are infected with hepatitis C virus (HCV). Acute hepatitis C is most often diagnosed in the setting of post-exposure surveillance, or seroconversion in high-risk individuals (eg, health-care professionals or injecting drug users) previously known to be seronegative. Although transmission via transfusion and injecting drug use has declined in developed countries, unsafe blood products and medical practices continue to increase transmission of HCV in many developing countries. Clinically, acute hepatitis C can increase concentrations of alanine aminotransferase to ten times the upper limit of normal but almost never causes fulminant hepatic failure. Diagnosis of HCV infection in the acute phase is difficult since production of antibodies against HCV can be delayed by up to 12 weeks, and about a third of infected individuals might not have detectable antibody at the onset of symptoms. Therefore, testing for HCV RNA by PCR is the only reliable test for the diagnosis of acute infection. Symptomatic patients with jaundice have a higher likelihood of spontaneous viral clearance than do asymptomatic patients, and thus should be monitored for at least 12 weeks before initiating antiviral therapy. By contrast, asymptomatic patients have a much lower chance of spontaneous clearance, and might benefit from early antiviral therapy. Antiviral therapy for 12 weeks is generally effective in treating patients who are HCV RNA negative after 4 weeks of treatment; lengthier courses could be needed for those who relapse or fail to show early virological clearance.

Biliary complications and outcomes of liver transplantation from donors after cardiac death

Biliary complications after liver transplantation (LT) using organs retrieved from donors after cardiac death are not well characterized. The aim of this study was to evaluate the severity of biliary complications and outcomes after donation after cardiac death liver transplantation (DCD‐LT). A retrospective evaluation of 20 DCD‐LTs from 1997–2006 was performed. The recipient age was 53 ± 8.7, and the donor age was 35 ± 11 years. The warm ischemia time, cold ischemia time, peak alanine aminotransferase level, and peak aspartate aminotransferase level were 33 ± 12 minutes, 8.7 ± 2.7 hours, 1757 ± 1477 U/L, and 4020 ± 3693 U/L, respectively. The bilirubin and alkaline phosphatase levels at hospital discharge after LT were 3.2 ± 5.4 mg/dL and 248 ± 200 U/L, respectively. During a median follow‐up of 7.5 months (range: 1–73), 5 patients (25%; 1 death after re‐LT) died (3 from sepsis, 1 from recurrent hepatocellular carcinoma at 4 months, and 1 from a cardiac event at 46 months), and additionally, 4 patients (20%) required re‐LT (1 because of hepatic artery thrombosis, 1 because of primary graft nonfunction, and 2 because of biliary strictures). Twelve (60%) developed biliary complications, and of these, 11 (55%) had serious biliary complications. The biliary complications were as follows: a major bile leak for 2 patients (10%; both eventually underwent retransplantation), anastomotic strictures for 5 patients (25%), hilar strictures for 7 patients (35%), extrahepatic donor duct strictures for 9 patients (45%), intrahepatic strictures for 10 patients (50%), stones for 1 patients (5%), casts for 7 patients (35%), and debris for 2 patients (10%). More than 1 biliary complication was seen in most patients, and these were unpredictable and required multiple diagnostic or therapeutic procedures. Serious biliary complications are common after DCD‐LT, and research should focus on identifying donor and recipient factors that predict and prevent serious biliary complications. Liver Transpl 13:1645–1653, 2007.

Long-Term Outcome of Liver Transplantation in Patients With PSC: A Comparative Analysis With PBC

BACKGROUND:Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are reported to have the best outcomes after liver transplantation. Based on excellent 5-yr survival results after transplantation, it has been suggested that PSC patients may benefit from “preemptive” transplantation to reduce the risk of cholangiocarcinoma. In this study, we compared 10-yr survival of patients with PSC and PBC using a large database after adjusting for other confounding risk factors.METHODS:The United Network for Organ Sharing (UNOS) database of all patients who had liver transplantation from 1987 to 2001 was used for analysis after excluding patients with multiple organ transplantation, children, and incomplete data.RESULTS:Patients with PSC (n = 3,309) were younger than those with PBC (n = 3,254). Retransplantation rate was high in PSC (12.4% vs 8.5%; p< 0.01), and PSC was an independent predictor for retransplantation on multivariate analysis. Cox regression analysis showed that PSC patients had significantly lower graft and patient survival compared to PBC patients after adjusting for other risk factors. Lower survival in PSC became apparent 7 yr after transplantation.CONCLUSIONS:Patients with PSC had a higher retransplantation rate and lower survival when compared to PBC. Based on this analysis, we do not recommend preemptive liver transplantation for patients with PSC.

Cryptogenic cirrhosis and NAFLD: are they related?

Cryptogenic cirrhosis (CC), literally meaning cirrhosis of obscure or unknown origin, is a diagnosis of exclusion. The circumstantial evidence indicates that nonalcoholic fatty liver disease (NAFLD) is perhaps one of the important causes of CC. There is also evidence, especially from the European literature, that some patients with CC may have undiagnosed or burnt-out autoimmune hepatitis (AIH). Other rare causes may include “unknown” viral (non-A, non-B, non-C) hepatitis, and occult alcoholism. In this review, we examine the role of NAFLD and other causes in the pathogenesis of CC, and the impact of obesity on patients with chronic liver disease.

A Randomized Controlled Trial of β-Blockers Versus Endoscopic Band Ligation for Primary Prophylaxis: A Large Sample Size is Required to Show a Difference in Bleeding Rates

Primary prophylaxis with nonselective β-blockers in high-risk subjects has been shown to be effective in reducing both esophageal variceal bleeding and mortality. Recently it has been suggested that band ligation may be a better option for primary prophylaxis. We compared nonselective β-blockers with band ligation in patients with large varices (F2, F3) and elevated hepatic venous wedge pressure gradient (HVWPG, ≥12 mm Hg). All patients were prospectively followed for variceal bleeding, mortality, and treatment-related complications. Based on previous published studies, we estimated that 90 patients in each arm would be required to show a difference in bleeding rate. The study was prematurely terminated when we realized that our estimated sample size was inadequate to show a difference based on the observed bleeding rate. At the time of termination, 31 patients (Child A, 11; B, 14; C, 6), with a mean HVWPG of 19 ± 9.1 mm Hg, were randomized to either band ligation (group A; n = 16) or β-blockers (group B; n = 15). Baseline demographics of both groups were similar and the mean follow-up period was 27.4 ± 12.9 months. During the follow-up, two patients in group A and one patient in group B had bleeding. Nine patients (29%; group A, six; group B, three; P = ns) died due to non-bleeding-related causes and five (16%) patients (group A, three; group B, two) underwent liver transplantation. Treatment-related complication were minimal in both groups. Despite the selection of high-risk patients, the observed bleeding rate was much lower than anticipated. Based on our observed bleeding rates, 424 patients would be required in each arm to show a difference between band ligation and β-blocker therapy.

Post-liver-transplant anemia: Etiology and management

Anemia is common after liver transplantation, with the incidence ranging from 4.3% to 28.2% depending on the criteria used to define anemia. The cause of anemia is unidentified in the majority of patients, and it is likely to be multifactorial. Immunosuppressive‐medication‐induced bone marrow suppression is perhaps the most common cause of unexplained anemia. Chronic blood loss, iron deficiency, hemolysis, and renal insufficiency are other potential causes of chronic anemia. Rare causes, somewhat unique to transplantation, include aplastic anemia, graft‐versus‐host disease (GVHD), and lymphoproliferative disease. Anemia due to immunosuppressive medication is challenging, since almost all drugs currently used for this purpose cause anemia, but the renal‐sparing property of sirolimus may benefit the subgroup in which renal insufficiency is contributing to anemia. Aplastic anemia is seen in young patients transplanted for non‐A, non‐B, non‐C, fulminant hepatic failure. It is thought to be immunologically mediated, secondary to an unknown viral infection, and is associated with a grave prognosis. GVHD is another infrequent (approximately 1% of transplant recipients) but serious cause of severe anemia that carries a dismal prognosis. Lymphoproliferative disorder, too may rarely rare cause anemia and it may respond to reduction of immunosuppression. Recipients of solid‐organ transplants do not mount a significant increase in erythropoietin in response to anemia. In conclusion, though there are no data on the response of anemia to erythropoietin in liver transplant recipients, it appears to benefit other solid‐organ‐transplant recipients with anemia. (Liver Transpl 2004;10:165–173.)

Management of Acute Hepatitis C

The World Health Organization estimates that about 170 million people are infected with hepatitis C virus (HCV). Blood transfusions from unscreened donors and unsafe therapeutic procedures are the major modes of HCV transmission in the developing world, and injection drug use accounts for most newly diagnosed HCV infections in the developed countries. Acute infection with HCV leads to symptomatic hepatitis in only a minority of patients, and recent studies suggest that spontaneous clearance of virus is higher in symptomatic acute hepatitis C infection. Pooled data from various studies suggest that higher sustained viral clearance rates could be achieved with a shorter course of antiviral treatment in the early stages of chronic HCV infection. This article examines the diagnosis of acute infection and critically appraises the various treatment regimens.

Endocrine Diseases and the Liver

Liver disease and endocrine disorders, both common in the general population, have a bidirectional and complex relationship. Certain liver diseases are more commonly associated with endocrine disorders, including nonalcoholic fatty liver disease, autoimmune hepatitis, and primary biliary cirrhosis. There may be an association between hepatitis C and type 2 diabetes mellitus as well as thyroid disorders, and sex hormonal preparations may cause specific hepatic lesions. The presence of relative adrenal insufficiency in patients with end-stage liver disease may have therapeutic implications in patients admitted with acute-on-chronic liver failure. The objective of this review is to focus on the effect of endocrine disorders on liver.

Survival after liver transplantation for hepatocellular carcinoma in the model for end‐stage liver disease and pre–model for end‐stage liver disease eras and the independent impact of hepatitis C virus

It has been suggested that hepatitis C virus (HCV) patients with hepatocellular carcinoma (HCC) may have worse outcomes after liver transplantation (LT) because of more aggressive tumor biology. In this study, we determined the post‐LT survival of HCC patients with and without HCV using United Network for Organ Sharing data from January 1994 to March 2008. Patients with HCC were stratified into HCV (HCC‐HCV) and non‐HCV (HCC–non‐HCV) groups. In the era before the Model for End‐Stage Liver Disease (MELD), there were 1237 HCC patients (780, HCV; 373, non‐HCV; 84, unknown HCV status), and during the MELD era, there were 4933 HCC patients (3272, HCV; 1348, non‐HCV; 313, unknown). In the pre‐MELD era, 5‐year graft (58.6% versus 53.7%) and patient (61.7% versus 59.3%) survival rates were marginally higher for HCC–non‐HCV patients than for HCC‐HCV patients. In the MELD era also, 5‐year graft (61.2% versus 55.5%) and patient (63.7% versus 58.2%) survival rates were marginally higher for HCC–non‐HCV patients than for HCC‐HCV patients. In patients without HCC, pre‐MELD and MELD era graft/patient survival rates for non‐HCV patients were higher than those for HCV patients. The differences in survival rates for HCC patients with and without HCV were lower than those for non‐HCC patients stratified by their HCV status. HCV had no additional negative impact on the post‐LT survival of patients with HCC, and this was further confirmed by multivariate analysis. In conclusion, the survival of HCC patients has remained unchanged in the past 2 decades. HCV patients have a lower survival rate than non‐HCV patients, regardless of their HCC status, but HCV has no additional negative impact on survival in patients with HCC. Liver Transpl 15:754–762, 2009.

Liver failure as initial presentation of autoimmune hepatitis: Clinical characteristics, predictors of response to steroid therapy, and outcomes

In a recent study, we had reported the impact of ethnicity on the natural history of autoimmune hepatitis (AIH).1 We did a further subgroup analysis of those with initial presentation with liver failure (LF), defined as either international normalized ratio (INR) ≥ 2 and or any degree of hepatic encephalopathy. Twenty patients (20/101, 19.8%) presented with LF, and they were more likely to be black (70% versus 7.4%, P = 0.001), require referral for liver transplantation (LT) (70% versus 24.6%, P < 0.0001), and have a higher mortality (45% versus 4.9%, P < 0.0001), compared to those without LF. Of the 14 (70%) patients with LF who were treated medically with steroids, seven (50%) responded (Table 1). Responders had a Model for End-Stage Liver Disease (MELD) score at admission ≤ 28 and were more likely to have cirrhosis (71.1% versus 28.5%); they showed a stable trend in serum bilirubin (mg/dL) (15.2 ± 13.2 versus 14.1 ± 14.1) and INR (1.8 ± 0.4 versus 1.8 ± 0.5) after a mean of 3.7 ± 0.6 days of steroid therapy. In contrast, nonresponders showed a worsening of serum bilirubin (22.5 ± 4.2 versus 23.1 ± 5.6) and INR (3.0 ± 1.5 versus 3.6 ± 2.1). All responders survived without need for a LT, whereas all nonresponders had a fatal outcome (of whom one died after LT). Six patients (30%) with LF were not treated medically, of whom five had submassive necrosis on liver biopsy. Five of these six patients underwent transplantation and all but one survived. One could not undergo transplantation due to development of fatal cholangitis.In conclusion, about 20% of patients with AIH have LF at initial presentation. A lower MELD score at admission (≤ 28), more severe hepatic fibrosis, and an early (within 4 days of steroid therapy) improvement or stabilization in serum bilirubin and INR identify those who are likely to respond to steroid therapy, and thus survive without LT. Our observations need further corroboration, but if confirmed, such a stratification strategy could optimize care of patients with AIH who present with LF.