K. V. Narayanan Menon

MELD accurately predicts mortality in patients with alcoholic hepatitis

Assessing severity of disease in patients with alcoholic hepatitis (AH) is useful for predicting mortality, guiding treatment decisions, and stratifying patients for therapeutic trials. The traditional disease‐specific prognostic model used for this purpose is the Maddrey discriminant function (DF). The model for end‐stage liver disease (MELD) is a more recently developed scoring system that has been validated as an independent predictor of patient survival in candidates for liver transplantation. The aim of the present study was to examine the ability of MELD to predict mortality in patients with AH. A retrospective cohort study of 73 patients diagnosed with AH between 1995 and 2001 was performed at the Mayo Clinic in Rochester, Minnesota. MELD was the only independent predictor of mortality in patients with AH. MELD was comparable to DF in predicting 30‐day mortality (c‐statistic and 95% CI: 0.83 [0.71‐0.96] and 0.74 [0.62‐0.87] for MELD and DF, respectively, not significant) and 90‐day mortality (c‐statistic and 95% CI: 0.86 [0.77‐0.96] and 0.83 [0.74‐0.92] for MELD and DF, respectively, not significant). A MELD score of 21 had a sensitivity of 75% and a specificity of 75% in predicting 90‐day mortality in AH. In conclusion, MELD is useful for predicting 30‐day and 90‐day mortality in patients with AH and maintains some practical and statistical advantages over DF in predicting mortality rate in these patients. MELD is a useful clinical tool for gauging mortality and guiding treatment decisions in patients with AH, particularly those complicated by ascites and/or encephalopathy. (HEPATOLOGY 2005;41:353–358.)

Bone disease in primary biliary cirrhosis: independent indicators and rate of progression

BACKGROUND/AIMS To identify indicators of osteoporosis and to determine the rate of bone loss in patients with primary biliary cirrhosis (PBC). METHODS Bone mineral density of the lumbar spine and hip was measured at annual intervals over 7 years of follow-up in 176 patients with PBC. RESULTS Osteoporosis (t-score below -2.5) was found in 20% of patients and occurred 32.1 times more frequently in patients with PBC than expected. Patients with histologic stage 3 or 4 disease had a 5.4-fold increased risk of osteoporosis compared to patients with stage 1 or 2. Age, body mass index, advanced stage (3 or 4), and history of fractures were the only independent indicators of osteoporosis. After 3 years of follow up, the rate of bone loss in patients with stage 1 or 2 increased and equaled that seen in patients with stage 3 or 4. Serum bilirubin level was the only variable independently associated with the rate of bone loss over time. CONCLUSIONS Severity of the liver disease contributes significantly to the severity of bone disease in PBC. PBC patients who are older, thinner and have more advanced liver disease may have the most benefit from bone density measurements and treatment for their osteoporosis.

MELD and Other Factors Associated with Survival after Liver Transplantation

Allocation of cadaveric livers for transplantation in the United States is now based on the severity of illness as determined by the model for end‐stage liver disease (MELD) score, a function of bilirubin, creatinine and international normalized ratio (INR). The aim of our study was to determine the association of various pre‐transplant risk factors, including the MELD score, on patient survival after orthotopic liver transplantation (OLT). The medical records of 499 consecutive patients (233 female, 266 males, mean age 50.9 ± 10.6 years) undergoing cadaveric OLT at our institution between June 1990 and February 1998 were reviewed. In the 407 patients alive at the latest contact, follow‐up was 4.7 years, with a minimum of 20 months (maximum of 9.4 years). Variables considered for analysis included MELD score, age, pre‐transplant renal dysfunction requiring dialysis, Child–Pugh classification, underlying liver disease, diabetes mellitus, and heart disease (ischemic/valvular/other). There were 92 deaths during follow‐up. In univariate analysis, the MELD score, renal failure requiring hemodialysis pre‐OLT, age > 42 years, and underlying etiology of liver disease were significantly associated with death during long‐term follow‐up. In multivariate models, age, underlying etiology of liver disease and renal failure requiring hemodialysis were independent predictors of death after OLT.

Pathogenesis, Diagnosis, and Treatment of Alcoholic Liver Disease

Alcohol-related liver disease is a major cause of morbidity and mortality in the United States. Alcoholic liver disease encompasses a clinicohistological spectrum, including fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. Fatty liver is a benign and reversible condition, but progression to alcoholic hepatitis and cirrhosis is life-threatening. Alcoholic hepatitis is diagnosed predominantly on clinical history, physical examination, and laboratory testing, although liver biopsy is often necessary to secure the diagnosis. The major focus of management is abstinence from alcohol, supportive care, treatment of complications of infection and portal hypertension, and maintenance of positive nitrogen balance through nutritional support. Corticosteroid therapy is controversial but should be considered in patients with a discriminant function greater than 32 and/or presence of spontaneous hepatic encephalopathy in the absence of infection, gastrointestinal bleeding, and renal failure. The only curative therapy for advanced alcoholic cirrhosis is liver transplantation. Several recent advances in understanding the pathogenesis of alcoholic liver disease may lead to novel future treatment approaches, including inhibition of tumor necrosis factor a, antioxidant therapy, stimulation of liver regeneration, and stimulation of collagen degradation.

A Pilot Study of the Safety and Tolerability of Etanercept in Patients with Alcoholic Hepatitis

BACKGROUND:Alcoholic hepatitis is a cause of major morbidity and mortality, and effective therapeutic regimens to treat this condition are lacking. Both experimental and clinical evidence indicates that tumor necrosis factor alpha (TNF), and the downstream cytokine interleukin-6 (IL-6), correlate with disease severity and may contribute to the pathogenesis and clinical sequelae of alcoholic hepatitis, thereby implicating a possible role for inhibition of TNF in the treatment of alcoholic hepatitis.OBJECTIVE:The aim of the current study was to assess the safety and tolerability of a p75-soluble TNF receptor:FC fusion protein (etanercept), an agent that binds and neutralizes soluble TNF in patients with alcoholic hepatitis in the form of an open-label pilot trial.METHODS:Etanercept administration was targeted for 2 wk duration in 13 patients with moderate or severe alcoholic hepatitis as assessed by a discriminant function value greater than 15 and/or the presence of spontaneous hepatic encephalopathy.RESULTS:On an intention-to-treat basis, the 30-day survival rate of patients receiving etanercept was 92% (12/13). Adverse events that were encountered included infection, hepatorenal decompensation, and GI bleeding, which required premature discontinuation of etanercept in 23% of patients (3/13).CONCLUSIONS:This is the first study to examine TNF inhibition with etanercept in patients with alcoholic hepatitis and the results of this study support the rationale for larger controlled studies to further assess safety and efficacy.

Comparative Analysis of the Safety and Efficacy of Transcatheter Arterial Chemoembolization and Yttrium-90 Radioembolization in Patients with Unresectable Hepatocellular Carcinoma

PURPOSE To compare retrospectively the safety and efficacy of yttrium-90 ((90)Y) radioembolization with the safety and efficacy of chemoembolization in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS Survival and complication rates were evaluated for patients with HCC who underwent chemoembolization or radioembolization at a single institution between August 2007 and April 2010. Complications were graded according to a standardized grading system for embolization procedures. Survival was determined via the Kaplan-Meier method, and multivariable analysis for factors affecting survival was performed. RESULTS This study included 73 patients with HCC who underwent index embolization with radioembolization (n = 38; 52.1%) or chemoembolization (n = 35; 47.9%). The two patient populations were similar in terms of demographics, etiology of cirrhosis, functional status, tumor characteristics, Child-Pugh class, previous liver-directed therapy, and number of patients with bilirubin > 2.0 mg/dL. There was no significant difference in survival between the radioembolization (median 8.0 months) and chemoembolization (median 10.3 months) cohorts (P = .33). Postembolization syndrome was significantly more severe in patients who underwent chemoembolization, which led to increased total hospitalization rates in these patients. The rates of other complications and rehospitalization were similar between groups. Increased age, Child-Pugh class B, hepatitis seropositivity, bilobar tumor distribution, tumor vascular invasion, and presence of extrahepatic metastases were associated with reduced patient survival. CONCLUSIONS Patients treated with radioembolization did not show a survival advantage over patients treated with chemoembolization. However, patients who underwent chemoembolization had significantly higher rates of hospitalization as a result of postembolization syndrome.

Analysis of factors that predict alcohol relapse following liver transplantation

Alcoholic liver disease has become a major indication for liver transplantation in the United States. Factors that predict alcohol relapse after liver transplantation are poorly defined. The aim of our study was to identify predictors of alcohol relapse in patients undergoing liver transplantation for alcoholic liver disease. One hundred and eleven patients undergoing liver transplantation for alcoholic liver disease between 1985 and 1999 were identified from our database. Patients were selected for liver transplantation if their risk of relapse was felt to be low by the transplant team. A chart review was conducted to determine if relapse had occurred, the presence or absence of factors that were thought to predict relapse, and survival. Demographic and psychosocial variables were analyzed using univariate and multivariate logistic regression to identify independent predictors of relapse. The median duration of abstinence before liver transplantation was 15 months (range: 1–120). Hepatitis C virus was present in 64% of patients. A family history of alcoholism in a first‐degree relative was identified in 38%, and 78% received treatment for alcoholism before liver transplantation. The mean duration of follow‐up was 44.1 ± 3.7 months. There were 29 deaths (26%) overall. Seventeen patients (15%) returned to alcohol use. On multivariate analysis a family history of alcoholism was found to be an independent predictor of alcohol relapse (P= .03). Further prospective studies are needed to examine this association in greater detail to provide targeted treatment for alcoholism both before and after liver transplantation. (Liver Transpl 2004;10:408–411.)

Hepatocellular carcinoma: From diagnosis to treatment.

Hepatocellular carcinoma (HCC) is the sixth most prevalent malignancy worldwide and is a rising cause of cancer related mortality. Risk factors for HCC are well documented and effective surveillance and early diagnosis allow for curative therapies. The majority of HCC appears to be caused by cirrhosis from chronic hepatitis B and hepatitis C virus. Preventive strategies include vaccination programs and anti-viral treatments. Surveillance with ultrasonography detects early stage disease and improves survival rates. Many treatment options exist for individuals with HCC and are determined by stage of presentation. Liver transplantation is offered to patients who are within the Milan criteria and are not candidates for hepatic resection. In patients with advanced stage disease, sorafenib shows some survival benefit.

Severe cholestatic hepatitis from troglitazone in a patient with nonalcoholic steatohepatitis and diabetes mellitus

Troglitazone is currently approved for the treatment of diabetes mellitus. Hepatic abnormalities have been reported in up to 1.9% of patients receiving the drug. Severe hepatotoxicity, including the need for liver transplantation, has also been reported in patients treated with troglitazone. Troglitazone has been reported to be beneficial in a small group of patients with nonalcoholic steatohepatitis (NASH). We present a patient with nonalcoholic steatohepatitis and diabetes mellitus who developed severe cholestasis after treatment with troglitazone. The exact mechanism of troglitazone toxicity is unknown, and whether preexisting liver abnormalities increase the incidence of toxicity is speculative. Further data are needed before more widespread use of troglitazone can be recommended for patients with nonalcoholic steatohepatitis.

Ultrasound-assisted percutaneous liver biopsy performed by a physician assistant

OBJECTIVE: Percutaneous liver biopsy is an essential diagnostic tool utilized in the management of patients with liver disease. This procedure is generally performed by a physician and has a small but well-defined complication rate. We report on the complication rate and efficiency of ultrasound-assisted percutaneous liver biopsy performed by an experienced physician assistant. METHODS: One thousand eighty-six consecutive outpatient liver biopsies (847 hepatic allografts and 239 native livers) were performed at a single center by a physician assistant between June, 1996 and June, 2000. Patients with hepatic mass lesions, unusual hepatic anatomy, and uncorrectable coagulopathy (international normalized ratio > 1.7, platelet count < 50 × 109/L) were excluded. Bedside ultrasonography was used to determine the optimal site for the liver biopsy. Liver biopsies were performed with a 15-gauge Jamshidi aspiration biopsy needle. Patients were observed for 3 h after biopsy, followed by dismissal with subsequent contact in 24 h to assess outcome and complications. RESULTS: Adequate tissue was obtained in 1084 cases (99.8%), with a mean tissue length of 3.2 cm. After the procedure, narcotic analgesia was necessary in 116 (10%) of the patients undergoing liver biopsies. The overall complication rate requiring hospitalization was 0.6%. Major complications requiring intervention occurred in four patients (0.4%). There were no deaths resulting from liver biopsies. CONCLUSION: We conclude that outpatient percutaneous liver biopsy can be safely and effectively performed by a trained physician assistant.