• Humans
• Liver Transplantation/standards
• Germany
• Gastroenterology/standards
• Practice Guidelines as Topic
• Societies, Medical

Among patients with severe polycystic liver disease (PLD) (height-adjusted total liver volume of <1800 ml/m), PKD2 variants were found in 34%. Three patients with PKD1 or PKD2 variants are reported with severe PLD but normal-sized kidneys (hTKV of < 250 ml/m).

Polycystic liver disease (PLD) is present in most patients with autosomal dominant polycystic kidney disease (ADPKD). PLD can alternatively be found with few, if any, kidney cysts as a diagnosis of isolated PLD (autosomal dominant PLD [ADPLD]). Several genes are identified as causative for this spectrum of phenotypes; however, the relative incidence of genetic etiologies among patients with severe PLD is unknown.

Patients with ADPKD or ADPLD having severe PLD defined as height-adjusted total liver volume (hTLV) >1800 ml/m were recruited. Subsequent clinical care was followed. Genetic analysis was performed using whole exome sequencing.

We enrolled and sequenced 49 patients (38 women, 11 men). Pathogenic or suspected pathogenic variants in polycystic disease genes were found in 44 of 49 patients (90%). The disease gene was PKD1 in 20 of 44 patients (45%), PKD2 in 15 of 44 patients (34%), PRKCSH in 5 of 44 patients (11%), GANAB in 2 of 44 patients (5%), SEC63 in 1 of 44 patients (2%), and ALG8 in 1 of 44 patients (2%). The median hTLV was no different between genetically defined ADPKD and ADPLD groups (4431 [range, 1817–9148] versus 3437 [range, 1860–8211]) ml, P = 0.77), whereas height-adjusted kidney volume was larger as expected in ADPKD than in ADPLD (607 [range, 190–2842] versus 179 [range, 138–234] ml/m, P < 0.01). Of the clinically defined ADPKD patients, 20 of 38 patients (53%) were PKD1 , 15 of 38 (39%) were PKD2 , and 3 (8%) remained genetically unsolved. Among patients with a pathogenic PKD1 or PKD2 variant, we found three patients with a liver-dominant ADPKD (severe PLD with height-adjusted total kidney volume <250 ml/m).

ADPLD-related genes represent 20% of patients with severe PLD in our cohort. Of those enrolled with ADPKD, we observed a higher frequency of PKD2 carriers than in any previously reported ADPKD cohorts. Although there was no significant difference in the hTLV between patients with PKD1 and PKD2 in this cohort, our data suggest that enrollment on the basis of severe PLD may enrich for patients with PKD2 .

• adpkd
• cystic kidney
• gene expression
• polycystic kidney disease

• Humans
• Japan
• Liver Diseases/genetics
• Cysts/genetics
• Cysts/pathology
• Female
• Male
• Genetic Testing
• Adult
• Mutation

• K08 DK119642 NIDDK NIH HHS
• UL1 TR001863 NCATS NIH HHS
• Okinaka Memorial Institute for Medical Research

• Computed tomography
• Focal liver lesions
• Imaging
• Magnetic resonance imaging
• Management
• Ultrasonography

• ADPKD
• ADPLD
• ARPKD
• Cystogenesis
• Liver cyst
• Mutation
• Polycystic liver disease

• Humans
• Liver Diseases/genetics
• Cysts/genetics
• Mutation/genetics

• Autosomal Dominant
• Genotype
• Polycystic Kidney
• Polycystic Liver Disease
• Risk Factors

• Adult
• Humans
• Female
• Male
• Polycystic Kidney, Autosomal Dominant/complications
• Polycystic Kidney, Autosomal Dominant/diagnosis
• Polycystic Kidney, Autosomal Dominant/genetics
• Liver
• Kidney
• Body Mass Index
• Laboratories

• 2019-ER-7304-00 Korea Disease Control and Prevention Agency
• 2019-ER-7304-01 Korea Disease Control and Prevention Agency
• 2019-ER-7304-02 Korea Disease Control and Prevention Agency

• Humans
• Quality of Life
• Liver Diseases/etiology
• Cysts/etiology

• efficacy
• embolization
• polycystic liver disease
• safety

• hepatomegaly
• liver
• liver cysts
• polycystic liver disease
• therapeutics

• funding

Polycystic liver disease (PLD) is a rare autosomal dominant disorder including two genetically and clinically distinct forms: autosomal dominant polycystic kidney disease (ADPKD) and isolated polycystic liver disease (PCLD). The main manifestation of ADPKD is kidney cysts, while PCLD has predominantly liver presentations with mild or absent kidney cysts. Over the past decade, PRKCSH, SEC63, ALG8, and LRP5 have been candidate genes of PCLD. Recently, more candidate genes such as GANAB, SEC61B, and ALR9 were also reported in PCLD patients. This review focused on all candidate genes of PCLD, including the newly established novel candidate genes. In addition, we also discussed some other genes which might also contribute to the disease.

• LRP5
• PCLD
• PLD
• PRKCSH
• Sec63
• alg8
• polycystic liver disease

Hepatic cyst infection is a complication of polycystic liver disease (PLD) that causes substantial morbidity. Repetitive infection is frequent and is increasingly difficult to treat. As translocated gut bacteria are considered the cause, we hypothesize that selective decontamination of the digestive tract (SDD) reduces recurrence of hepatic cyst infection.

We performed a retrospective, observational study in two referral centres. All patients with PLD treated with SDD for hepatic cyst infection were included. Efficacy was determined by calculating the infection incidence (hepatic cyst infections per month) before and during SDD therapy. Adverse events were scored according to the Common Terminology Criteria for Adverse Events (CTCAE).

We identified eight patients who received SDD (88% female, 88% polycystic kidney disease). The median age was 65 years (IQR: 51–74 years). SDD lowered the median incidence from 0.09 episodes per month (IQR: 0.06–0.25 episodes per month) to 0.01 episodes per month (IQR: 0.00–0.05 episodes per month) (P = 0.12). Discontinuation of SDD led to rapid recurrence of cyst infection (71% within 6 weeks). SDD consisted of polymyxins with/without aminoglycosides. The median SDD treatment duration was 20 months (range: 3–89 months). Six patients (75%) developed adverse events [CTCAE Grade 1 (gastrointestinal: n = 3) or Grade 3 (ototoxicity: n = 1; fungal infection: n = 1)], mostly attributable to aminoglycosides; one patient developed polymyxin E resistance.

SDD prophylaxis provides a novel strategy for limiting recurrent hepatic cyst infection in PLD patients. However, adverse events are frequent and curtail its use. As most were attributable to aminoglycosides, polymyxin E is considered the preferred therapy.

• Cyst-liver area ratio
• Drenth classification
• Gigot classification
• Liver cyst indicator
• Maximum liver cyst diameter
• Mutation type
• Nonsense mutation
• PKD1
• Polycystic liver disease
• Polycystin-1
• Sex difference
• Substitution mutation

Autosomal dominant polycystic liver disease (ADPLD) is characterized by multiple cysts in the liver without (or only occasional) renal cysts. At least seven genes are associated with high risk for developing ADPLD; however, clear genetic involvement is undetermined in more than 50% of ADPLD patients.

To identify additional ADPLD-associated genes, we collected 18 unrelated Chinese ADPLD cases, and performed whole exome sequencing on all the participants. After filtering the sequencing data against the human gene mutation database (HGMD) professional edition, we identified new mutations. We then sequenced this gene in family members of the patient.

Among the 18 ADPLD cases analyzed by whole exome sequencing, we found 2 cases with a PRKCSH mutation (~11.1%), 2 cases with a PKD2 mutation (~11.1%), 1 case with both PKHD1 and PKD1 mutations (~5.6%), 1 case with GANAB mutation (~5.6%), 1 case with PKHD1 mutation (~5.6%), and 1 case with PKD1 mutations (~5.6%). We identified a new PKHD1 missense mutation in an ADPLD family, in which both patients showed innumerable small hepatic cysts, as reported previously. Additionally, we found that PRKCSH and SEC63 mutation frequencies were lower in the Chinese population compared with those in European and American populations.

We report a family with ADPLD associated with a novel PKHD1 mutation (G1210R). The genetic profile of ADPLD in the Chinese population is different from that in European and American populations, suggesting that further genetic research on genetic mutation of ADPLD in the Chinese population is warranted.

• Autosomal dominant polycystic liver disease (ADPLD)
• PKHD1
• genetic profile
• new gene mutation

Isolated autosomal-dominant polycystic liver disease (ADPLD) is generally considered a rare disease. However, the frequency of truncating mutations to ADPLD genes in large, population sequencing databases is 1:496. With the increasing use of abdominal imaging, incidental detection of hepatic cysts and ADPLD has become more frequent. The present study was performed to ascertain the incidence and point prevalence of ADPLD in Olmsted County, MN, USA, and how these are impacted by the increasing utilisation of abdominal imaging.

The Rochester Epidemiology Project and radiology databases of Mayo Clinic and Olmsted Medical Center were searched to identify all subjects meeting diagnostic criteria for definite, likely, or possible ADPLD. Annual incidence rates were calculated using incident cases during 1980–2016 as numerator, and age- and sex-specific estimates of the population of Olmsted County as denominator. Point prevalence was calculated using prevalence cases as numerator, and age- and sex-specific estimates of the population of Olmsted County on 1 January 2010 as denominator.

The incidence rate and point prevalence of combined definite and likely ADPLD were 1.01 per 100,000 person-years and 9.5 per 100,000 population, respectively. Only 15 of 35 definite and likely incident ADPLD cases had received a diagnostic code, and only 8 had clinically significant hepatomegaly. The incidence rates were much higher when adding possible cases, mainly identified through radiology databases, particularly in recent years and in older patients because of the increased utilisation of imaging studies.

Clinically significant isolated ADPLD is a rare disease with a prevalence <1:10,000 population. The overall prevalence of ADPLD, however, to a large extent not clinically significant, is likely much higher and closer to the reported genetic prevalence.

Isolated autosomal-dominant polycystic liver disease (ADPLD) is generally considered a rare disease. However, we demonstrate that it is a relatively common disease, which is rarely (<1:10,000 population) clinically significant.

•

Isolated autosomal-dominant polycystic liver disease (ADPLD) is generally considered a rare disease.

• ADPKD, autosomal-dominant polycystic kidney disease
• ADPLD, autosomal-dominant polycystic liver disease
• Autosomal-dominant polycystic liver disease
• CT, computed tomography
• Epidemiology
• Hepatic cysts
• HtLV, liver volume adjusted by height
• IQR, inter-quartile range
• Incidence
• Liver imaging
• MRI, magnetic resonance imaging
• PLD, polycystic liver disease
• Polycystic liver disease
• Prevalence
• US, ultrasound

• Cholangiocytes
• Glucosidase II
• Liver cysts
• Molecular inversion probe analysis
• Polycystic liver disease

The Polycystic Kidney Disease (PKD) is characterized by progressive renal cyst development and other extrarenal manifestation including Polycystic Liver Disease (PLD). Phenotypical characterization of animal models mimicking human diseases are commonly used, in order to, study new molecular mechanisms and identify new therapeutic approaches. The main biomarker of disease progression is total volume of kidney and liver in both human and mouse, which correlates with organ function. For this reason, the estimation of the number and area of the tissue occupied by cysts, is critical for the understanding of physiological mechanisms underlying the disease. In this regard, cystic index is a robust parameter commonly used to quantify the severity of the disease. To date, the vast majority of biomedical researchers use ImageJ as a software tool to estimate the cystic index by quantifying the cystic areas of histological images after thresholding. This tool has imitations of being inaccurate, largely due to incorrectly identifying non-cystic regions. We have developed a new software, named CystAnalyser (register by Universidade de Santiago de Compostela–USC, and Fundación Investigación Sanitaria de Santiago—FIDIS), that combines automatic image processing with a graphical user friendly interface that allows investigators to oversee and easily correct the image processing before quantification. CystAnalyser was able to generate a cystic profile including cystic index, number of cysts and cyst size. In order to test the CystAnalyser software, 795 cystic kidney, and liver histological images were analyzed. Using CystAnalyser there were no differences calculating cystic index automatically versus user input, except in specific circumstances where it was necessary for the user to distinguish between mildly cystic from non-cystic regions. The sensitivity and specificity of the number of cysts detected by the automatic quantification depends on the type of organ and cystic severity, with values 76.84–78.59% and 76.96–89.66% for the kidney and 87.29–93.80% and 63.42–86.07% for the liver. CystAnalyser, in addition, provides a new tool for estimating the number of cysts and a more specific measure of the cystic index than ImageJ. This study proposes CystAnalyser is a new robust and freely downloadable software tool for analyzing the severity of disease by quantifying histological images of cystic organs for routine biomedical research. CystAnalyser can be downloaded from https://citius.usc.es/transferencia/software/cystanalyser (for Windows and Linux) for research purposes.

This work suggests CystAnalyser is the most reliable software tool currently available for the assessment of cystic pathologies including Polycystic Kidney Disease (PKD) and Polycystic Liver Disease (PLD). CystAnalyser combines automatic cyst recognition with a friendly graphical user interface, allowing user input prior to histological image quantification. CystAnalyser responds to the need to obtain reliable measurements of the universal biomarker for PKD and PLD disease progression, the Cystic index (area of cysts within the total area of tissue). This software tool is also able to calculate the number and size of cysts from the histological images. In summary, our results show that CystAnalyser overcomes the precision issues detected using the most commonly used software to date (ImageJ) for Cystic index quantification, offering users a reliable tool to easily characterize the phenotype and the pathophysiology of PKD and PLD in pre-clinical studies using animal models.

• Autosomal dominant polycystic kidney disease
• autosomal dominant polycystic liver disease
• estrogen
• hepatic cystogenesis
• liver cyst
• mTOR
• metformin
• polycystic liver disease
• somatostatin
• tolvaptan

• Animals
• Autophagy/drug effects
• Cysts/drug therapy
• Cysts/physiopathology
• Female
• Humans
• Liver Diseases/drug therapy
• Liver Diseases/physiopathology
• MicroRNAs/metabolism
• Molecular Targeted Therapy
• Polycystic Kidney Diseases/drug therapy
• Polycystic Kidney Diseases/physiopathology
• Signal Transduction/drug effects
• Wnt Signaling Pathway/drug effects

Polycystic liver disease (PLD) is a rare hereditary disease that independently exists in isolated PLD, or as an accompanying symptom of autosomal dominant polycystic kidney disease and autosomal recessive polycystic kidney disease with complicated mechanisms. PLD currently lacks a unified diagnostic standard. The diagnosis of PLD is usually made when the number of hepatic cysts is more than 20. Gigot classification and Schnelldorfer classification are now commonly used to define severity in PLD. Most PLD patients have no clinical symptoms, and minority with severe complications need treatments. Somatostatin analogues, mammalian target of rapamycin inhibitor, ursodeoxycholic acid and vasopressin-2 receptor antagonist are the potentially effective medical therapies, while cyst aspiration and sclerosis, transcatheter arterial embolization, fenestration, hepatic resection and liver transplantation are the options of invasion therapies. However, the effectiveness of these therapies except liver transplantation are still uncertain. Furthermore, there is no unified strategy to treat PLD between medical centers at present. In order to better understand recent study progresses on PLD for clinical practice and obtain potential directions for future researches, this review mainly focuses on the recent progress in PLD classification, clinical manifestation, diagnosis and treatment. For information, we also provided medical treatment processes of PLD in our medical center.

• Polycystic liver disease
• Autosomal dominant polycystic kidney disease
• Autosomal recessive polycystic kidney disease
• Isolated polycystic liver disease
• Diagnosis
• Treatment

• cystic liver
• poly-cystic kidney disease
• ventral hernia

• Drug
• Liver Size
• Polycystic Liver Disease
• Somatostatin Analogues

• Adult
• Cysts/diagnostic imaging
• Cysts/drug therapy
• Cysts/etiology
• Cysts/pathology
• Drug Administration Schedule
• Female
• Humans
• Injections, Subcutaneous
• Kidney/diagnostic imaging
• Kidney/drug effects
• Kidney/pathology
• Liver/diagnostic imaging
• Liver/drug effects
• Liver/pathology
• Liver Diseases/diagnostic imaging
• Liver Diseases/drug therapy
• Liver Diseases/etiology
• Liver Diseases/pathology
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Organ Size/drug effects
• Peptides, Cyclic/administration & dosage
• Polycystic Kidney, Autosomal Dominant/complications
• Polycystic Kidney, Autosomal Dominant/diagnostic imaging
• Polycystic Kidney, Autosomal Dominant/drug therapy
• Somatostatin/administration & dosage
• Somatostatin/analogs & derivatives
• Treatment Outcome

To describe first episodes of bacterial cholangitis complicating autosomal dominant polycystic kidney disease (ADPKD) and autosomal dominant polycystic liver disease (ADPLD) and to identify risk factors for cholangitis episodes among patients with ADPKD-associated polycystic liver disease (PLD).

We searched the electronic medical records at our tertiary referral center for episodes of cholangitis in patients with ADPKD or ADPLD from January 1, 1996, through June 30, 2017. Cases were categorized as suspected or definite cholangitis by expert review. Clinical, laboratory, and radiologic data were manually abstracted. A nested case-control study was conducted to investigate risk factors for cholangitis in patients with ADPKD.

We identified 29 cases of definite or suspected cholangitis complicating PLD (24 with ADPKD-associated PLD and 5 with ADPLD). Among patients with definite cholangitis in ADPKD-associated PLD (n=19) vs ADPLD (n=4), the mean ± SD age was 62.4±12.2 vs 55.1±8.6 years, and 9 (47.4%) vs 0 (0%), respectively, were male. The odds of gallstones (odds ratio [OR], 21.6; 95% CI, 3.17-927; P<.001), prior cholecystectomy (OR, 12.2; 95% CI, 1.59-552; P=.008), duodenal diverticulum (OR, 13.5; 95% CI, 2.44 to not estimable; P=.004), type 2 diabetes mellitus (OR, 6.41; 95% CI, 1.01 to not estimable; P=.05), prior endoscopic retrograde cholangiopancreatography (OR, 14.0; 95% CI, 1.80-631; P=.005), and prior kidney transplant (OR, 8.06; 95% CI, 1.72-76.0; P=.004) were higher in patients with ADPKD-associated PLD with definite cholangitis compared to controls.

Gallstones, prior cholecystectomy, duodenal diverticulosis, type 2 diabetes mellitus, prior endoscopic retrograde cholangiopancreatography, and prior kidney transplant constituted risk factors for cholangitis among patients with ADPKD-associated PLD.

• ADPKD, autosomal dominant polycystic kidney disease
• ADPLD, autosomal dominant polycystic liver disease
• ALP, alkaline phosphatase
• ALT, alanine aminotransferase
• AST, aspartate aminotransferase
• CT, computed tomography
• ERCP, endoscopic retrograde cholangiopancreatography
• ICD-10, International Classification of Diseases,Tenth Revision
• ICD-9, International Classification of Diseases,Ninth Revision
• MCR, Mayo Clinic, Rochester, MN
• MRI, magnetic resonance imaging
• OR, odds ratio
• PET, positron emission tomography
• PLD, polycystic liver disease
• T2DM, type 2 diabetes mellitus

• ADPKD
• ADPLD
• polycystic liver disease
• risk factors

• Aneurysm
• Angiosarcoma
• Femoral artery
• Polycystic kidney

• Aged
• Aneurysm/complications
• Aneurysm/diagnosis
• Biomarkers, Tumor/analysis
• Biopsy
• Cysts/complications
• Cysts/diagnosis
• Femoral Artery/chemistry
• Femoral Artery/pathology
• Hemangiosarcoma/chemistry
• Hemangiosarcoma/complications
• Hemangiosarcoma/secondary
• Humans
• Immunohistochemistry
• Liver Diseases/complications
• Liver Diseases/diagnosis
• Lung Neoplasms/chemistry
• Lung Neoplasms/complications
• Lung Neoplasms/secondary
• Lymphatic Metastasis
• Polycystic Kidney Diseases/complications
• Polycystic Kidney Diseases/diagnosis
• Vascular Neoplasms/chemistry
• Vascular Neoplasms/complications
• Vascular Neoplasms/pathology

• ADPKD
• Hemodialysis
• Liver cyst infection
• Liver transplantation
• Polycystic kidney disease
• Polycystic liver disease

• Clinical management
• Complications
• Liver cysts
• Liver volume
• PLD-Q
• POLCA
• Polycystic liver disease
• Quality of life
• Treatment

• Adult
• Cysts/complications
• Cysts/diagnosis
• Cysts/etiology
• Cysts/therapy
• Female
• Genetic Counseling
• Genetic Testing
• Humans
• Liver/pathology
• Liver Diseases/complications
• Liver Diseases/diagnosis
• Liver Diseases/etiology
• Liver Diseases/therapy

• Autosomal dominant polycystic kidney disease (ADPKD)
• autosomal dominant polycystic liver disease (ADPLD)
• hepatomegaly
• quality of life
• symptoms

• Liver cysts
• Polycystic liver disease

• Polycystic liver disease
• liver transplantation
• pharmacological therapies
• somatostatin analogues
• ursodeoxycholic acid

• ADPKD
• Cysts
• Diverticulosis
• Hernia

Although polycystic liver disease (PCLD) is one of the extrarenal complications in patients with autosomal dominant polycystic kidney disease (ADPKD), longitudinal changes and the association with total liver volume (TLV) have not been clearly elucidated yet.

Patients with ADPKD were chosen who underwent computed tomography or magnetic resonance imaging twice or more during August 2003 through December 2015. TLV, each cyst volume, and the proportion of parenchyma were measured. The natural history of liver cysts and the association between TLV and liver cysts were evaluated. To compare with liver cysts in ADPKD patients with PCLD, simple liver cysts in patients without ADPKD were also evaluated.

TLV at baseline and its growth rate in all the patients with ADPKD, whose serum creatinine, estimated glomerular filtration rate, and total kidney volume were 1.45 mg/dl (0.76–2.32 mg/dl), 38.5 ml/min per 1.73 m² (18.7–57.9 ml/min per 1.73 m²), and 1394 ml (773–2861 ml), were 1431 ml (1062–1749 ml) and −0.95%/yr (−3.16 to 4.94%/yr), respectively, in the observation period (median, 1063 days). Neither TLV nor its growth rate was significantly different between ADPKD patients with PCLD and those without PCLD. The growth rate of 79 liver cysts was 39.5%/yr (17.5–80.8%/yr) in PCLD patients with ADPKD. It was significantly larger than that of 60 simple liver cysts in the non-ADPKD group, 11.0%/yr (−2.2 to 33.1%/yr). Moreover, the proportion of parenchyma reduced, whereas that of total cyst volume increased significantly (P = 0.001).

The reduction of parenchyma was accompanied by the growth of liver cysts during time course in PCLD patients with ADPKD.

• autosomal dominant polycystic kidney disease
• polycystic liver disease

• Autosomal dominant polycystic kidney disease
• CT volumetry
• Polycystic liver disease
• Quality of life
• Ursodeoxycholic acid

• Cysts
• Humans
• Liver Diseases
• Polycystic Kidney, Autosomal Dominant
• Quality of Life
• Ursodeoxycholic Acid

• congenital liver cyst
• laparoscopic fenestration
• laparoscopic hepatic resection
• polycystic liver disease (pld)

• ADPKD
• ADPLD
• alkaline phosphatase
• drug therapy
• hepatic cyst
• somatostatin

• Adult
• Aged
• Alkaline Phosphatase/blood
• Biomarkers/blood
• Clinical Trials as Topic
• Cysts/blood
• Cysts/diagnostic imaging
• Cysts/drug therapy
• Female
• Humans
• Linear Models
• Liver/diagnostic imaging
• Liver/drug effects
• Liver/enzymology
• Liver Diseases/blood
• Liver Diseases/diagnostic imaging
• Liver Diseases/drug therapy
• Logistic Models
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Multivariate Analysis
• Octreotide/therapeutic use
• Organ Size
• Peptides, Cyclic/therapeutic use
• Predictive Value of Tests
• Somatostatin/analogs & derivatives
• Somatostatin/therapeutic use
• Time Factors
• Tomography, X-Ray Computed
• Treatment Outcome

• P30 DK090728 NIDDK NIH HHS
• R01 DK044863 NIDDK NIH HHS

• Isolated polycystic liver disease
• Liver cyst
• Polycystic liver
• Rupture

• Adult
• Cysts/drug therapy
• Cysts/psychology
• Double-Blind Method
• Female
• Humans
• Liver Diseases/drug therapy
• Liver Diseases/psychology
• Male
• Middle Aged
• Organ Size
• Polycystic Kidney, Autosomal Dominant/drug therapy
• Polycystic Kidney, Autosomal Dominant/psychology
• Quality of Life
• Somatostatin/analogs & derivatives
• Treatment Outcome