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Biomedical subjects

Morris Sherman

Publications and source records attributed to Morris Sherman.

At least 19 recordsLinked to original sources
PubMed2006

Chronic hepatitis C and screening for hepatocellular carcinoma.

It is now at least theoretically possible to prevent patients with hepatocellular carcinoma (HCC) from dying of HCC. Screening identifies small potentially curable lesions, and the diagnostic algorithm allows for efficient investigation and diagnosis. Radiofrequency ablation completely ablates more than 05% of lesions smaller than 2 cm. Second primary cancers can be dealt with in the same manner as the initial primary. If the management of HCC is so efficient and effective, liver transplantation may come to be used as a last resort, rather than the treatment of choice. This benefits patients with hepatitis C and other liver diseases because more organs become available for treatment of other liver diseases.

Carcinoma, Hepatocellular↗
PubMed2006

Entecavir for treatment of lamivudine-refractory, HBeAg-positive chronic hepatitis B.

BACKGROUND & AIMS: Lamivudine treatment is associated with frequent development of resistant hepatitis B virus (HBV) and loss of treatment benefit. In preclinical and phase II studies, entecavir demonstrated potent antiviral activity against lamivudine-resistant HBV. METHODS: In this phase III, double-blind trial, hepatitis B e antigen-positive patients who were refractory to lamivudine therapy (persistent viremia or documented YMDD mutations while receiving lamivudine) were randomized to switch to entecavir 1 mg daily (n = 141) or continue lamivudine 100 mg daily (n = 145) for a minimum of 52 weeks. Two coprimary end points were assessed at 48 weeks: histologic improvement and a composite end point (HBV branched DNA <0.7 MEq/mL and alanine aminotransferase [ALT] <1.25 times the upper limit of normal). RESULTS: Histologic improvement occurred in 55% (68/124) of entecavir-treated vs 28% (32/116) of lamivudine-treated patients (P < .0001). More patients on entecavir than lamivudine achieved the composite end point: 55% (77/141) vs 4% (6/145), respectively (P < .0001). Mean change from baseline in HBV DNA was -5.11 log(10) copies/mL for entecavir-treated patients and -0.48 log(10) copies/mL for lamivudine-treated patients (P < .0001). Virologic rebound because of entecavir resistance substitutions occurred in 2 of 141 of entecavir-treated patients, and genotypic evidence of resistance was detected in 10 patients. The safety profile of entecavir was comparable to lamivudine with fewer ALT flares on treatment. CONCLUSIONS: In patients with lamivudine-refractory chronic hepatitis B, switching to entecavir provides superior histologic improvement, viral load reduction, and ALT normalization compared with continuing lamivudine, with a comparable adverse event profile.

Adolescent↗
PubMed2006

Optimizing management strategies in special patient populations.

Chronic hepatitis B infection presents a number of challenges to clinicians. There are additional considerations when defining management strategies for individuals with advanced liver disease, or coinfection, or those at high risk of developing hepatocellular carcinoma (HCC). Treatment of decompensated cirrhosis is particularly important. Evidence suggests that suppression of viral replication through nucleos(t)ide analog therapy leads to longer time to transplantation, improved liver function, and improved survival times. The use of interferon in patients with decompensated hepatitis B is associated with serious complications and is currently contraindicated for these patients by the AASLD Practice Guidelines. Hepatitis B coinfection is often associated with more extensive disease. In patients with HBV/HCV coinfection, one disease is usually dominant and consequently should be the focus of therapy. HIV/HBV coinfection increases the risk of progressive liver disease. Therapeutic agents active against both viruses should be utilized at the correct dose to limit the development of resistance. Agents specific for HBV, e.g., entecavir, enable hepatitis to be treated while avoiding the risk of HIV resistance developing. Dual infection with HBV and HDV is particularly challenging. Nucleos(t)ide analogs are ineffective in treating HDV infection, and there is limited data concerning the efficacy of interferon in this setting. The association between chronic hepatitis B infection and hepatocellular carcinoma (HCC) is well established. In patients at high risk of HCC, screening regimes may be effective. Furthermore, there is an increasing body of evidence indicating that effective suppression of viral replication may be associated with a reduced risk of HCC.

Antiviral Agents↗
PubMed2006

Advancing patient care: integrating new data.

Physicians involved in the management of patients with chronic hepatitis B infection are frequently faced with complex clinical issues concerning the diagnosis, investigation, and treatment of patients. Guidelines exist within the literature that help with decision making; however, in practice individual nuances are often encountered necessitating decisions that go beyond the current guidelines. Following presentation of the available data, a panel of expert hepatologists and gastroenterologists sought to identify and solve challenges that are faced by clinicians in the daily management of patients with chronic hepatitis B infection. The following summary provides an overview of the outcome of these discussions. Because of the complexities of clinical management, the recommendations reflect the opinion of the majority; however, many recommendations were not unanimous. Furthermore, the recommendations that follow are limited to adult patients; the treatment of children was not discussed. A number of issues were identified, and statements concerning possible management strategies that could be applied were developed.

Hepatitis B, Chronic↗
PubMed2006

Clinical recommendations for the use of recombinant human erythropoietin in patients with hepatitis C virus being treated with ribavirin.

Today, combination antiviral therapy with pegylated interferon-alpha and ribavirin (RBV) allows many patients infected with hepatitis C virus (HCV) to achieve a sustained virological response, which is equivalent to cure. Data also support the clinical benefit of combination antiviral therapy in patients coinfected with HCV and HIV, and in patients who have received a liver transplant. Antiviral therapy with pegylated interferon-alpha and RBV is, however, associated with a high incidence and significant magnitude of anemia. This anemia may have several mechanisms, including bone marrow suppression and hemolysis. In addition, patients coinfected with HIV may have both pre-existing and RBV-associated anemia. Management of anemia in patients with HCV through RBV dose reduction or treatment discontinuation may compromise the effectiveness of treatment, because studies have demonstrated that treatment adherence or maintenance of antiviral therapy dose is an important predictor of sustained virological response. Anemia associated with combination antiviral therapy in patients with HCV is frequently associated with an inadequate or blunted endogenous erythropoietin response. Accumulating evidence now supports the use of recombinant human erythropoietin (rHuEpo) to manage anemia in these patients, with the objective of maintaining the RBV dose, but clinical standards are lacking. The present article reviews the data relevant to the use of rHuEpo in this patient population and proposes a set of clinical practice standards to assist clinicians in selecting patients for rHuEpo and in implementing rHuEpo therapy effectively.

Algorithms↗
PubMed2005

Approaches to the diagnosis of hepatocellular carcinoma.

The advent of screening programs for hepatocellular carcinoma in patients with chronic viral hepatitis and cirrhosis has resulted in detection of smaller and smaller lesions in the liver. Some of these are small carcinomas, but many are not malignant in nature or are potential precursors to malignancy. Neither radiology nor biopsy can be used confidently to distinguish between these possibilities when the lesions are smaller than approximately 1.5 cm in diameter. Therefore, diagnostic algorithms must be developed to assist physicians in investigating these small lesions and deciding when they are truly malignant, when treatment is necessary, or whether a watchful waiting course is appropriate. The diagnostic difficulties are presented, with examples of diagnostic algorithms that may be helpful in managing these patients.

Biomarkers, Tumor↗
PubMed2005

Screening for hepatocellular carcinoma.

There is currently no evidence that screening patients at risk for hepatocellular carcinoma reduces mortality from the disease. Nonetheless, screening is widely practiced. Screening is a process that includes selecting patients, applying screening tests, deciding on recall policies, and subsequently proving or disproving the presence of cancer. The literature on screening for hepatocellular carcinoma is confusing at best, and does not adequately consider the many biases that result from uncontrolled and retrospective studies. Nonetheless, screening can be justified because it is likely that mortality is decreased by adequate treatment of small cancers, particularly in the era of liver transplantation. False-positive screening test results are common. Once an abnormal screening result is obtained there is little guidance from the literature as to how patients should be investigated further, nor about how to determine whether the screening test result was a false-positive. This should at minimum include short interval follow-up with CT scans and MRI's.

Age Factors↗
PubMed2005

Hepatocellular carcinoma: epidemiology, risk factors, and screening.

In this article, the epidemiology of hepatocellular carcinoma (HCC), risk factors for the development of HCC, and how these factors affect the decision about whether an individual should or should be entered into a screening program are considered. The factors determining the risk for HCC include age, male gender, and the nature of the underlying liver disease. In particular, cirrhosis is associated with a significant risk for HCC. However, in hepatitis B HCC also occurs in noncirrhotic liver. Decision analysis can be used to identify patients at greatest risk for HCC and who might be candidates for screening. Screening itself should be developed in a programmatic manner to ensure that appropriate target populations are identified, that appropriate screening tests are chosen, and that appropriate recall and enhanced follow-up are instituted for patients who have positive screening test results. Screening should be by ultrasonography at 4- to 12-month intervals. Patients with abnormal screening tests require additional investigation using computed tomography scanning, magnetic resonance imaging, or liver biopsy. Negative results do not exclude the possibility of cancer and further follow-up is necessary.

Age Factors↗
PubMed2005

Simple clinical variables predict liver histology in hepatitis C: prospective validation of a clinical prediction model.

OBJECTIVE: A recent single-center multivariate analysis of hepatitis C (HCV) patients showed that having any two criteria: 1) ferritin > or =200 microg/l and 2) spider nevi and/or albumin < or = 35 g/l predicted grade 2 or greater histological inflammation; the presence of any two of the following criteria: spider nevi, platelets < or =150 x 109/l, palpable splenomegaly and/or albumin < or =35 g/l predicted stage 2 or greater histological fibrosis. Absence of predictors also predicted a lack of inflammation and fibrosis. Our aim was prospectively to validate this clinical prediction model using an independent multicenter sample. MATERIAL AND METHODS: Eighty-one patients with previously untreated active chronic HCV underwent physical examination, laboratory investigation, and liver biopsy. Biopsies were read, in blinded fashion, by a single pathologist, using a modified Hytiroglou (1995) scale. The clinical scoring system was correlated with histology; likelihood ratios (LRs), Fisher's exact p-values, and receiver operating characteristics (ROCs) were calculated. RESULTS: Data recording was complete in 77 and 38 patients regarding fibrotic stage and inflammatory grade, respectively. For fibrosis, 3/3 patients with any three criteria (LR 17, positive predictive value (PPV) 100%), 4/5 patients with any two criteria (LR 5.1), and 15/47 with no criteria (LR 0.6, negative predictive value (NPV) 68%) had stage 2 or greater fibrosis on biopsy (p=0.01). For inflammation, 5/5 patients with both criteria (LR 15, PPV 100%), and 8/19 patients with no criteria (LR 0.5, NPV 58%) had moderate-severe inflammation on liver biopsy (p=0.036). When missing variables were assumed to be normal, recalculated LRs were almost identical. An alanine aminotransferase (ALAT) level <60 U/l may increase the NPVs. CONCLUSIONS: This independent multicenter data set has validated our published model which uses simple clinical variables accurately and significantly to predict hepatic fibrosis and inflammation in HCV patients.

Adult↗
PubMed2005

Needle tract seeding after radiofrequency ablation of hepatic tumors.

PURPOSE: To determine the incidence and risk factors associated with needle tract seeding after radiofrequency ablation (RFA) of liver tumors. MATERIALS AND METHODS: A prospective data base of patients with hepatic tumors treated by RFA from December 1999 until August 2003 was reviewed to identify patients with needle tract seeding. During this period, 200 patients (148 men, 52 women) with 299 lesions underwent 298 treatment sessions. Patients with both primary (153 hepatocellular carcinoma, two cholangiocarcinoma) and a variety of secondary tumors (35 colorectal, 10 other) were treated. RFA was performed percutaneously with computed tomography (CT) and/or ultrasound (US) guidance, or with US guidance at laparoscopy or laparotomy. All procedures were performed with a LeVeen needle electrode. The needle tract was not routinely coagulated or embolized. RESULTS: Eight patients out of 200 (4%) were identified with needle tract seeding, based on imaging findings or surgical reintervention. This corresponds to a rate of eight of 298 (2.7%) per treatment session and eight of 299 (2.7%) per lesion. Statistically significant risk factors for neoplastic seeding included treatment of a subcapsular lesion (OR = 11.57, P = .007), multiple treatment sessions (OR = 2.0, P = .037), and multiple electrode placements (OR = 1.4, P = .006). CONCLUSIONS: Neoplastic seeding may occur after RFA of liver tumors. The results show that the frequency of this complication is not insignificant, and are at the upper end of rates reported in the literature of 0.5% to 2.8%. Specific risk factors identified in this study include treatment of subcapsular lesions, patients treated in multiple sessions, and lesions requiring more than one electrode placement.

Adult↗
PubMed2005

Outcome of small (10-20 mm) arterial phase-enhancing nodules seen on triphasic liver CT in patients with cirrhosis or chronic liver disease.

OBJECTIVE: To determine the outcome of small arterial phase-enhancing nodules, 10-20 mm, seen on serial triphasic liver CT scans in a hepatocellular cancer-screening population. METHODS: Of 58 patients referred for triphasic liver CT, 20 (18 men, 2 women) with 32 nodules formed the study group. Each patient in the study group had at least two CT scans, a minimum of 3 months follow-up, at least one nodule measuring 10-20 mm, no prior diagnosis of hepatocellular carcinoma, and no nodule greater than 20 mm typical of hepatocellular carcinoma at the time of the first CT. Serial CT scans were reviewed by an abdominal imaging radiologist who classified the nodules as stable, decreasing, or increasing in size. RESULTS: A mean of six CT studies (range 2-10) were performed for each patient with a mean follow-up of 25 months (range 4-47 months). Of 32 nodules, 14 (44%) were stable, 9 (28%) decreased, and 9 (28%) increased in size. Nodules that increased in size were treated as hepatocellular carcinoma: six were hepatocellular carcinoma, two were biopsy negative but showed recurrent tumor after radiofrequency ablation, and one was a high-grade dysplastic nodule. Mean doubling time for these nine nodules was 5.7 months (range 2.3-10.8 months). CONCLUSIONS: Most small (10-20 mm) arterial phase-enhancing nodules seen on triphasic liver CT are not hepatocellular carcinoma. Serial CT is useful to guide management in these patients. Growth of small arterial phase-enhancing nodules can be used as an indicator that the nodule should be treated as hepatocellular carcinoma.

Aged↗
PubMed2004

Pathogenesis and screening for hepatocellular carcinoma.

Hepatocellular carcinoma is an increasingly common clinical problem. Investigators have begun to understand aspects of the pathogenesis of the tumor, mainly from a morphologic point of view. Preneoplastic lesions and early cancer may be difficult to distinguish radiologically. Nonetheless, programs for surveillance of liver cancer have been developed. Little uniformity exists in methods of surveillance, and even less in methods of investigation and follow-up after an abnormal result is obtained. This article attempts to bring some rigor to the understanding of hepatocellular carcinoma.

Carcinoma, Hepatocellular↗